IDH-mutated acute myeloid leukemia is characterized by mutations in isocitrate dehydrogenase genes IDH1 (6-10% of AML) or IDH2 (8-12% of AML). These mutations confer neomorphic enzymatic activity, producing the oncometabolite 2-hydroxyglutarate (2-HG) instead of alpha-ketoglutarate. Elevated 2-HG inhibits alpha-ketoglutarate- dependent dioxygenases, causing epigenetic dysregulation and differentiation block. The development of targeted IDH inhibitors (ivosidenib for IDH1, enasidenib for IDH2) represents a paradigm of metabolic-targeted cancer therapy, inducing differentiation rather than cytotoxicity.
Ask a research question about Acute Myeloid Leukemia, IDH-Mutated. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Acute Myeloid Leukemia, IDH-Mutated
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-04-22T20:13:21Z'
description: >-
IDH-mutated acute myeloid leukemia is characterized by mutations in isocitrate
dehydrogenase genes IDH1 (6-10% of AML) or IDH2 (8-12% of AML). These mutations
confer neomorphic enzymatic activity, producing the oncometabolite 2-hydroxyglutarate
(2-HG) instead of alpha-ketoglutarate. Elevated 2-HG inhibits alpha-ketoglutarate-
dependent dioxygenases, causing epigenetic dysregulation and differentiation block.
The development of targeted IDH inhibitors (ivosidenib for IDH1, enasidenib for
IDH2)
represents a paradigm of metabolic-targeted cancer therapy, inducing differentiation
rather than cytotoxicity.
categories:
- Hematologic Malignancy
- Acute Leukemia
- Molecularly Defined Cancer
- Metabolic Cancer
parents:
- acute myeloid leukemia
has_subtypes:
- name: IDH1-Mutated AML
description: >-
AML with mutations in cytoplasmic IDH1, most commonly R132H. IDH1 mutations
occur in 6-10% of AML cases and are targetable with ivosidenib. Often
co-occurs with NPM1 and DNMT3A mutations.
- name: IDH2-Mutated AML
description: >-
AML with mutations in mitochondrial IDH2, either R140Q (more common) or R172K.
IDH2 mutations occur in 8-12% of AML cases and are targetable with enasidenib.
R172K mutations may have different clinical features than R140Q.
pathophysiology:
- name: IDH Neomorphic Enzyme Activity
description: >-
Wild-type IDH1 and IDH2 convert isocitrate to alpha-ketoglutarate in the
cytoplasm and mitochondria respectively. Mutant IDH enzymes gain neomorphic
activity, reducing alpha-ketoglutarate to the oncometabolite 2-hydroxyglutarate
(2-HG), which accumulates to millimolar concentrations in leukemic cells.
evidence:
- reference: PMID:37526143
reference_title: "The curious case of IDH mutant acute myeloid leukaemia: biochemistry and therapeutic approaches."
supports: SUPPORT
evidence_source: OTHER
snippet: "Mutations in isocitrate dehydrogenase (IDH) 1 and -2 increase the capacity of cancer cells to produce a normally scarce metabolite, D-2-hydroxyglutarate (2-HG), by several orders of magnitude."
explanation: This abstract links IDH1/2 mutations to increased 2-HG production, supporting the neomorphic IDH activity described.
cell_types:
- preferred_term: myeloblast
term:
id: CL:0000835
label: myeloblast
downstream:
- target: 2-HG Accumulation
description: Oncometabolite accumulates to high levels in leukemic cells
- name: 2-HG Accumulation
description: >-
Mutant IDH enzymes produce the oncometabolite 2-HG at markedly increased levels,
leading to its accumulation in leukemic cells.
evidence:
- reference: PMID:37526143
reference_title: "The curious case of IDH mutant acute myeloid leukaemia: biochemistry and therapeutic approaches."
supports: SUPPORT
evidence_source: OTHER
snippet: "Mutations in isocitrate dehydrogenase (IDH) 1 and -2 increase the capacity of cancer cells to produce a normally scarce metabolite, D-2-hydroxyglutarate (2-HG), by several orders of magnitude."
explanation: This review supports marked accumulation of the oncometabolite 2-HG in IDH-mutant AML.
downstream:
- target: Dioxygenase Inhibition
description: Accumulated 2-HG inhibits alpha-KG-dependent enzymes
- name: Dioxygenase Inhibition
description: >-
2-HG is structurally similar to alpha-ketoglutarate and competitively inhibits
alpha-ketoglutarate-dependent dioxygenases. Key targets include TET2 DNA
demethylases, Jumonji-domain histone demethylases, and prolyl hydroxylases.
This disrupts normal epigenetic regulation and hypoxia responses.
evidence:
- reference: PMID:37526143
reference_title: "The curious case of IDH mutant acute myeloid leukaemia: biochemistry and therapeutic approaches."
supports: SUPPORT
evidence_source: OTHER
snippet: "2-HG dysregulates a wide array of molecular pathways, among them a large family of dioxygenases that utilise the closely related metabolite α-ketoglutarate (α-KG) as an essential co-substrate."
explanation: Review article confirms that 2-HG inhibits a broad family of α-ketoglutarate-dependent dioxygenases, the mechanistic basis of the IDH-mutant epigenetic phenotype.
biological_processes:
- preferred_term: DNA demethylation
modifier: DECREASED
term:
id: GO:0141166
label: chromosomal 5-methylcytosine DNA demethylation pathway
downstream:
- target: DNA Hypermethylation
description: TET2 inhibition causes aberrant DNA methylation
- target: Histone Methylation Dysregulation
description: JmjC demethylase inhibition alters histone marks
- name: DNA Hypermethylation
description: >-
Inhibition of TET2 by 2-HG impairs the conversion of 5-methylcytosine to
5-hydroxymethylcytosine, disrupting active DNA demethylation. This causes
hypermethylation at gene promoters, silencing differentiation genes and
contributing to the leukemic phenotype.
biological_processes:
- preferred_term: myeloid cell differentiation
modifier: DECREASED
term:
id: GO:0030099
label: myeloid cell differentiation
downstream:
- target: Differentiation Block
description: Epigenetic silencing of differentiation genes maintains blast state
- name: Histone Methylation Dysregulation
description: >-
2-HG inhibits Jumonji-domain histone demethylases that remove methyl groups
from lysine residues on histones. This causes accumulation of repressive
histone marks and altered gene expression patterns contributing to
leukemogenesis.
molecular_functions:
- preferred_term: histone demethylase activity
modifier: DECREASED
term:
id: GO:0032452
label: histone demethylase activity
- name: Differentiation Block
description: >-
The combined epigenetic effects of 2-HG on DNA methylation and histone
modifications block normal myeloid differentiation, maintaining leukemic
cells in an immature blast state. IDH inhibitors can overcome this block,
inducing differentiation of leukemic blasts.
cell_types:
- preferred_term: myeloid cell
term:
id: CL:0000763
label: myeloid cell
locations:
- preferred_term: bone marrow
term:
id: UBERON:0002371
label: bone marrow
histopathology:
- name: Myeloblast Predominance
finding_term:
preferred_term: Myeloblasts Present
term:
id: NCIT:C155995
label: Myeloblasts Present
frequency: VERY_FREQUENT
description: Acute myeloid leukemia features increased myeloblasts in blood or marrow.
evidence:
- reference: PMID:23590662
reference_title: "Acute myeloid leukemia: advances in diagnosis and classification."
supports: SUPPORT
snippet: "myeloblasts in the blood or bone marrow."
explanation: Abstract notes myeloblasts in the blood or bone marrow in AML.
phenotypes:
- category: Hematologic
name: Anemia
frequency: VERY_FREQUENT
description: >-
Normocytic anemia from bone marrow replacement by leukemic blasts
and ineffective erythropoiesis.
phenotype_term:
preferred_term: Anemia
term:
id: HP:0001903
label: Anemia
- category: Hematologic
name: Thrombocytopenia
frequency: VERY_FREQUENT
description: >-
Low platelet count due to bone marrow infiltration.
phenotype_term:
preferred_term: Thrombocytopenia
term:
id: HP:0001873
label: Thrombocytopenia
- category: Hematologic
name: Leukocytosis
frequency: FREQUENT
description: >-
Elevated white blood cell count with circulating blasts, though
IDH-mutated AML may present with lower blast counts than other subtypes.
phenotype_term:
preferred_term: Leukocytosis
term:
id: HP:0001974
label: Increased total leukocyte count
- category: Constitutional
name: Fatigue
frequency: VERY_FREQUENT
description: >-
Fatigue from anemia and hypermetabolic state.
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
- category: Infectious
name: Recurrent Infections
frequency: FREQUENT
description: >-
Susceptibility to infections from neutropenia and immune dysfunction.
phenotype_term:
preferred_term: Recurrent infections
term:
id: HP:0002719
label: Recurrent infections
biochemical:
- name: 2-Hydroxyglutarate Levels
notes: >-
2-HG can be measured in serum or bone marrow and is markedly elevated in
IDH-mutated AML. Levels correlate with disease burden and decrease with
effective IDH inhibitor therapy. Serves as a pharmacodynamic biomarker.
- name: IDH1/IDH2 Mutation Testing
notes: >-
PCR-based assays or next-generation sequencing detect IDH1 R132 and IDH2
R140/R172 mutations. Testing is essential for therapy selection given
the availability of targeted inhibitors.
genetic:
- name: IDH1
association: Somatic Oncogenic Mutation
notes: >-
Mutations at R132 in IDH1 (most commonly R132H) occur in 6-10% of AML.
IDH1 encodes the cytoplasmic isocitrate dehydrogenase. Mutations create
neomorphic enzyme activity producing 2-HG. Targetable with ivosidenib.
- name: IDH2
association: Somatic Oncogenic Mutation
notes: >-
Mutations at R140 (most common) or R172 in IDH2 occur in 8-12% of AML.
IDH2 encodes the mitochondrial isocitrate dehydrogenase. Mutations
create neomorphic enzyme activity. Targetable with enasidenib.
treatments:
- name: Ivosidenib
description: >-
Selective IDH1 inhibitor approved for newly diagnosed and relapsed/refractory
IDH1-mutated AML. Induces differentiation of leukemic blasts by reducing 2-HG
levels. Can be used as monotherapy or combined with azacitidine. Differentiation
syndrome is a manageable toxicity.
treatment_term:
preferred_term: targeted therapy
term:
id: NCIT:C93352
label: Targeted Therapy
therapeutic_agent:
- preferred_term: ivosidenib
term:
id: CHEBI:145430
label: ivosidenib
- name: Enasidenib
description: >-
Selective IDH2 inhibitor approved for relapsed/refractory IDH2-mutated AML.
Induces differentiation by suppressing 2-HG production. Effective in patients
who have failed multiple prior therapies. Differentiation syndrome requires
monitoring.
treatment_term:
preferred_term: targeted therapy
term:
id: NCIT:C93352
label: Targeted Therapy
therapeutic_agent:
- preferred_term: enasidenib
term:
id: CHEBI:145374
label: enasidenib
- name: Venetoclax plus Azacitidine
description: >-
BCL2 inhibitor venetoclax with hypomethylating agent is effective in
IDH-mutated AML, which is particularly sensitive to this combination.
IDH mutations may predict enhanced venetoclax sensitivity.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: venetoclax
term:
id: CHEBI:133021
label: venetoclax
- name: Intensive Chemotherapy (7+3)
description: >-
Standard induction chemotherapy achieves complete remission in many
IDH-mutated AML patients. Can be combined with IDH inhibitors for
enhanced efficacy.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
- name: Allogeneic Stem Cell Transplantation
description: >-
Consolidation option for eligible patients in first remission,
particularly those with adverse risk features beyond IDH mutation alone.
treatment_term:
preferred_term: hematopoietic stem cell transplantation
term:
id: MAXO:0000747
label: hematopoietic stem cell transplantation
disease_term:
preferred_term: IDH-mutated acute myeloid leukemia
term:
id: MONDO:0018874
label: acute myeloid leukemia
classifications:
icdo_morphology:
classification_value: Leukemia
harrisons_chapter:
- classification_value: cancer
- classification_value: hematologic malignancy
references:
- reference: DOI:10.1002/ajh.26822
title: 'Acute myeloid leukemia: 2023 update on diagnosis, risk‐stratification, and management'
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: Disease overviewAcute myeloid leukemia (AML) is a frequently fatal bone marrow stem cell cancer characterized by unbridled proliferation of malignant marrow stem cells with associated infection, anemia, and bleeding.
supporting_text: Disease overviewAcute myeloid leukemia (AML) is a frequently fatal bone marrow stem cell cancer characterized by unbridled proliferation of malignant marrow stem cells with associated infection, anemia, and bleeding.
evidence:
- reference: DOI:10.1002/ajh.26822
reference_title: 'Acute myeloid leukemia: 2023 update on diagnosis, risk‐stratification, and management'
supports: SUPPORT
evidence_source: OTHER
snippet: Disease overviewAcute myeloid leukemia (AML) is a frequently fatal bone marrow stem cell cancer characterized by unbridled proliferation of malignant marrow stem cells with associated infection, anemia, and bleeding.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.1016/j.stem.2013.12.016
title: Proto-Oncogenic Role of Mutant IDH2 in Leukemia Initiation and Maintenance
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: Proto-Oncogenic Role of Mutant IDH2 in Leukemia Initiation and Maintenance
supporting_text: Proto-Oncogenic Role of Mutant IDH2 in Leukemia Initiation and Maintenance
- reference: DOI:10.1038/s41375-024-02246-2
title: Management of isocitrate dehydrogenase 1/2 mutated acute myeloid leukemia
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: The emergence of next generation sequencing and widespread use of mutational profiling in acute myeloid leukemia (AML) has broadened our understanding of the heterogeneous molecular basis of the disease.
supporting_text: The emergence of next generation sequencing and widespread use of mutational profiling in acute myeloid leukemia (AML) has broadened our understanding of the heterogeneous molecular basis of the disease.
evidence:
- reference: DOI:10.1038/s41375-024-02246-2
reference_title: Management of isocitrate dehydrogenase 1/2 mutated acute myeloid leukemia
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The emergence of next generation sequencing and widespread use of mutational profiling in acute myeloid leukemia (AML) has broadened our understanding of the heterogeneous molecular basis of the disease.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.1038/s41388-023-02611-y
title: Transgenic IDH2R172K and IDH2R140Q zebrafish models recapitulated features of human acute myeloid leukemia
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: Isocitrate dehydrogenase 2 (IDH2) mutations occur in more than 15% of cytogenetically normal acute myeloid leukemia (CN-AML) but comparative studies of their roles in leukemogenesis have been scarce.
supporting_text: Isocitrate dehydrogenase 2 (IDH2) mutations occur in more than 15% of cytogenetically normal acute myeloid leukemia (CN-AML) but comparative studies of their roles in leukemogenesis have been scarce.
evidence:
- reference: DOI:10.1038/s41388-023-02611-y
reference_title: Transgenic IDH2R172K and IDH2R140Q zebrafish models recapitulated features of human acute myeloid leukemia
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: Isocitrate dehydrogenase 2 (IDH2) mutations occur in more than 15% of cytogenetically normal acute myeloid leukemia (CN-AML) but comparative studies of their roles in leukemogenesis have been scarce.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.1038/s41408-021-00497-1
title: 'Acute myeloid leukemia with IDH1 and IDH2 mutations: 2021 treatment algorithm'
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: Acute myeloid leukemia is a genetically heterogeneous hematologic malignancy; approximately 20% of AML harbors a mutation in the isocitrate dehydrogenase (IDH) genes, IDH1 or IDH2.
supporting_text: Acute myeloid leukemia is a genetically heterogeneous hematologic malignancy; approximately 20% of AML harbors a mutation in the isocitrate dehydrogenase (IDH) genes, IDH1 or IDH2.
evidence:
- reference: DOI:10.1038/s41408-021-00497-1
reference_title: 'Acute myeloid leukemia with IDH1 and IDH2 mutations: 2021 treatment algorithm'
supports: SUPPORT
evidence_source: OTHER
snippet: Acute myeloid leukemia is a genetically heterogeneous hematologic malignancy; approximately 20% of AML harbors a mutation in the isocitrate dehydrogenase (IDH) genes, IDH1 or IDH2.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.1038/s41408-024-01143-2
title: Current status and research directions in acute myeloid leukemia
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: Current status and research directions in acute myeloid leukemia
supporting_text: Current status and research directions in acute myeloid leukemia
- reference: DOI:10.1038/s41409-023-02189-9
title: Persistent IDH mutations are not associated with increased relapse or death in patients with IDH-mutated acute myeloid leukemia undergoing allogeneic hematopoietic cell transplant with post-transplant cyclophosphamide
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: Persistent IDH mutations are not associated with increased relapse or death in patients with IDH-mutated acute myeloid leukemia undergoing allogeneic hematopoietic cell transplant with post-transplant cyclophosphamide
supporting_text: Persistent IDH mutations are not associated with increased relapse or death in patients with IDH-mutated acute myeloid leukemia undergoing allogeneic hematopoietic cell transplant with post-transplant cyclophosphamide
- reference: DOI:10.1080/10428194.2022.2140288
title: Cost-effectiveness of azacitidine and ivosidenib in newly diagnosed older, intensive chemotherapy-ineligible patients with <i>IDH1</i> -mutant acute myeloid leukemia
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: Cost-effectiveness of azacitidine and ivosidenib in newly diagnosed older, intensive chemotherapy-ineligible patients with <i>IDH1</i> -mutant acute myeloid leukemia
supporting_text: Cost-effectiveness of azacitidine and ivosidenib in newly diagnosed older, intensive chemotherapy-ineligible patients with <i>IDH1</i> -mutant acute myeloid leukemia
- reference: DOI:10.1158/1078-0432.ccr-20-0834
title: 'Differentiation Syndrome with Ivosidenib and Enasidenib Treatment in Patients with Relapsed or Refractory IDH-Mutated AML: A U.S. Food and Drug Administration Systematic Analysis'
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: 'Differentiation syndrome (DS) is a serious adverse reaction of isocitrate dehydrogenase (IDH) inhibitors ivosidenib and enasidenib in patients with (IDH)1- and IDH2-mutated acute myeloid leukemia (AML), respectively.'
supporting_text: 'Differentiation syndrome (DS) is a serious adverse reaction of isocitrate dehydrogenase (IDH) inhibitors ivosidenib and enasidenib in patients with (IDH)1- and IDH2-mutated acute myeloid leukemia (AML), respectively.'
evidence:
- reference: DOI:10.1158/1078-0432.ccr-20-0834
reference_title: 'Differentiation Syndrome with Ivosidenib and Enasidenib Treatment in Patients with Relapsed or Refractory IDH-Mutated AML: A U.S. Food and Drug Administration Systematic Analysis'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: 'Differentiation syndrome (DS) is a serious adverse reaction of isocitrate dehydrogenase (IDH) inhibitors ivosidenib and enasidenib in patients with (IDH)1- and IDH2-mutated acute myeloid leukemia (AML), respectively.'
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.1158/1078-0432.ccr-21-3467
title: Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and <i>IDH1/2</i> Mutations
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: 'To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML).'
supporting_text: 'To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML).'
evidence:
- reference: DOI:10.1158/1078-0432.ccr-21-3467
reference_title: Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and <i>IDH1/2</i> Mutations
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: 'To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML).'
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.1182/blood-2018-08-869008
title: Molecular remission and response patterns in patients with mutant-IDH2 acute myeloid leukemia treated with enasidenib
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: Approximately 8% to 19% of patients with acute myeloid leukemia (AML) have isocitrate dehydrogenase-2 (IDH2) mutations, which occur at active site arginine residues R140 and R172.
supporting_text: Approximately 8% to 19% of patients with acute myeloid leukemia (AML) have isocitrate dehydrogenase-2 (IDH2) mutations, which occur at active site arginine residues R140 and R172.
evidence:
- reference: DOI:10.1182/blood-2018-08-869008
reference_title: Molecular remission and response patterns in patients with mutant-IDH2 acute myeloid leukemia treated with enasidenib
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Approximately 8% to 19% of patients with acute myeloid leukemia (AML) have isocitrate dehydrogenase-2 (IDH2) mutations, which occur at active site arginine residues R140 and R172.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.1182/bloodadvances.2021005789
title: Impact of<i>IDH1</i>and<i>IDH2</i>mutation detection at diagnosis and in remission in patients with AML receiving allogeneic transplantation
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: Somatic mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are common in acute myeloid leukemia (AML).
supporting_text: Somatic mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are common in acute myeloid leukemia (AML).
evidence:
- reference: DOI:10.1182/bloodadvances.2021005789
reference_title: Impact of<i>IDH1</i>and<i>IDH2</i>mutation detection at diagnosis and in remission in patients with AML receiving allogeneic transplantation
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Somatic mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are common in acute myeloid leukemia (AML).
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.1182/bloodadvances.2022008632
title: Enasidenib as maintenance following allogeneic hematopoietic cell transplantation for <i>IDH2</i>-mutated myeloid malignancies
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: IDH2 (isocitrate dehydrogenase 2) mutations occur in approximately 15% of patients with acute myeloid leukemia (AML).
supporting_text: IDH2 (isocitrate dehydrogenase 2) mutations occur in approximately 15% of patients with acute myeloid leukemia (AML).
evidence:
- reference: DOI:10.1182/bloodadvances.2022008632
reference_title: Enasidenib as maintenance following allogeneic hematopoietic cell transplantation for <i>IDH2</i>-mutated myeloid malignancies
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: IDH2 (isocitrate dehydrogenase 2) mutations occur in approximately 15% of patients with acute myeloid leukemia (AML).
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.1186/s13148-023-01529-2
title: 'Efficacy and safety of FDA-approved IDH inhibitors in the treatment of IDH mutated acute myeloid leukemia: a systematic review and meta-analysis'
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML).
supporting_text: To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML).
evidence:
- reference: DOI:10.1186/s13148-023-01529-2
reference_title: 'Efficacy and safety of FDA-approved IDH inhibitors in the treatment of IDH mutated acute myeloid leukemia: a systematic review and meta-analysis'
supports: SUPPORT
evidence_source: OTHER
snippet: To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML).
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.3389/fonc.2021.639387
title: IDH1/IDH2 Inhibition in Acute Myeloid Leukemia
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: IDH1/IDH2 Inhibition in Acute Myeloid Leukemia
supporting_text: Recently, the discovery of biological and clinical properties of mutated isoforms 1 and 2 mutations of isocitrate dehydrogenases (IDH) 1 and 2, affecting approximately 20% of patients with acute myeloid leukemia (AML), lead to the development of an individualized treatment strategy.
evidence:
- reference: DOI:10.3389/fonc.2021.639387
reference_title: IDH1/IDH2 Inhibition in Acute Myeloid Leukemia
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Recently, the discovery of biological and clinical properties of mutated isoforms 1 and 2 mutations of isocitrate dehydrogenases (IDH) 1 and 2, affecting approximately 20% of patients with acute myeloid leukemia (AML), lead to the development of an individualized treatment strategy.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.3389/fphar.2024.1489045
title: A real-world study of adverse drug reactions of two isocitrate dehydrogenase inhibitor based on the US FDA adverse event reporting system and VigiAccess databases
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: A real-world study of adverse drug reactions of two isocitrate dehydrogenase inhibitor based on the US FDA adverse event reporting system and VigiAccess databases
supporting_text: and objectivesIsocitrate dehydrogenase (IDH) inhibitor drugs (Enasidenib, Ivosidenib) restore normal metabolism and epigenetic regulation in cells, offering a precision-targeted therapeutic option for acute myeloid leukemia (AML) patients with IDH mutations by specifically inhibiting mutated IDH enzymes.
evidence:
- reference: DOI:10.3389/fphar.2024.1489045
reference_title: A real-world study of adverse drug reactions of two isocitrate dehydrogenase inhibitor based on the US FDA adverse event reporting system and VigiAccess databases
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: and objectivesIsocitrate dehydrogenase (IDH) inhibitor drugs (Enasidenib, Ivosidenib) restore normal metabolism and epigenetic regulation in cells, offering a precision-targeted therapeutic option for acute myeloid leukemia (AML) patients with IDH mutations by specifically inhibiting mutated IDH enzymes.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.3390/cancers12092427
title: Isocitrate Dehydrogenase Mutations in Myelodysplastic Syndromes and in Acute Myeloid Leukemias
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: Acute myeloid leukemia (AML) is a heterogeneous disease generated by the acquisition of multiple genetic and epigenetic aberrations which impair the proliferation and differentiation of hematopoietic progenitors and precursors.
supporting_text: Acute myeloid leukemia (AML) is a heterogeneous disease generated by the acquisition of multiple genetic and epigenetic aberrations which impair the proliferation and differentiation of hematopoietic progenitors and precursors.
evidence:
- reference: DOI:10.3390/cancers12092427
reference_title: Isocitrate Dehydrogenase Mutations in Myelodysplastic Syndromes and in Acute Myeloid Leukemias
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Acute myeloid leukemia (AML) is a heterogeneous disease generated by the acquisition of multiple genetic and epigenetic aberrations which impair the proliferation and differentiation of hematopoietic progenitors and precursors.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.3390/cancers15113002
title: Paradigm Shift in the Management of Acute Myeloid Leukemia—Approved Options in 2023
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: The word Leukemia was coined nearly 200 years ago by Rudolf Virchow.
supporting_text: The word Leukemia was coined nearly 200 years ago by Rudolf Virchow.
evidence:
- reference: DOI:10.3390/cancers15113002
reference_title: Paradigm Shift in the Management of Acute Myeloid Leukemia—Approved Options in 2023
supports: SUPPORT
evidence_source: OTHER
snippet: The word Leukemia was coined nearly 200 years ago by Rudolf Virchow.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.3390/cancers15184573
title: Mechanisms of Resistance to Small Molecules in Acute Myeloid Leukemia
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: In recent years, great progress has been made in the therapy of AML by targeting cellular processes associated with specific molecular features of the disease.
supporting_text: In recent years, great progress has been made in the therapy of AML by targeting cellular processes associated with specific molecular features of the disease.
evidence:
- reference: DOI:10.3390/cancers15184573
reference_title: Mechanisms of Resistance to Small Molecules in Acute Myeloid Leukemia
supports: SUPPORT
evidence_source: OTHER
snippet: In recent years, great progress has been made in the therapy of AML by targeting cellular processes associated with specific molecular features of the disease.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.3390/cancers16152675
title: The Leukemic Isocitrate Dehydrogenase (IDH) 1/2 Mutations Impair Myeloid and Erythroid Cell Differentiation of Primary Human Hematopoietic Stem and Progenitor Cells (HSPCs)
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: How hematopoietic stem and progenitor cell (HSPC) fate decisions are affected by genetic alterations acquired during AML leukemogenesis is poorly understood and mainly explored in animal models.
supporting_text: How hematopoietic stem and progenitor cell (HSPC) fate decisions are affected by genetic alterations acquired during AML leukemogenesis is poorly understood and mainly explored in animal models.
evidence:
- reference: DOI:10.3390/cancers16152675
reference_title: The Leukemic Isocitrate Dehydrogenase (IDH) 1/2 Mutations Impair Myeloid and Erythroid Cell Differentiation of Primary Human Hematopoietic Stem and Progenitor Cells (HSPCs)
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: How hematopoietic stem and progenitor cell (HSPC) fate decisions are affected by genetic alterations acquired during AML leukemogenesis is poorly understood and mainly explored in animal models.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.3390/cells13161392
title: 'Common Driver Mutations in AML: Biological Impact, Clinical Considerations, and Treatment Strategies'
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: Next-generation sequencing of samples from patients with acute myeloid leukemia (AML) has revealed several driver gene mutations in adult AML.
supporting_text: Next-generation sequencing of samples from patients with acute myeloid leukemia (AML) has revealed several driver gene mutations in adult AML.
evidence:
- reference: DOI:10.3390/cells13161392
reference_title: 'Common Driver Mutations in AML: Biological Impact, Clinical Considerations, and Treatment Strategies'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Next-generation sequencing of samples from patients with acute myeloid leukemia (AML) has revealed several driver gene mutations in adult AML.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
- reference: DOI:10.3390/ijms25137337
title: Molecular Targeting of the Isocitrate Dehydrogenase Pathway and the Implications for Cancer Therapy
found_in:
- IDH_Mutant_AML-deep-research-falcon.md
findings:
- statement: The advent of comprehensive genomic profiling using next-generation sequencing (NGS) has unveiled an abundance of potentially actionable genetic aberrations that have shaped our understanding of the cancer biology landscape.
supporting_text: The advent of comprehensive genomic profiling using next-generation sequencing (NGS) has unveiled an abundance of potentially actionable genetic aberrations that have shaped our understanding of the cancer biology landscape.
evidence:
- reference: DOI:10.3390/ijms25137337
reference_title: Molecular Targeting of the Isocitrate Dehydrogenase Pathway and the Implications for Cancer Therapy
supports: SUPPORT
evidence_source: OTHER
snippet: The advent of comprehensive genomic profiling using next-generation sequencing (NGS) has unveiled an abundance of potentially actionable genetic aberrations that have shaped our understanding of the cancer biology landscape.
explanation: Deep research cited this publication as relevant literature for IDH Mutant AML.
AML is an aggressive marrow/blood cancer characterized by clonal proliferation of malignant hematopoietic blasts leading to marrow failure, commonly presenting with anemia, infections, and bleeding due to cytopenias. (shimony2023acutemyeloidleukemia pages 1-2, premnath2023paradigmshiftin pages 1-2)
“IDH‑mutated AML” refers to AML cases harboring somatic hotspot missense mutations in IDH1 or IDH2 that drive malignant transformation via production of the oncometabolite (R/D)-2‑hydroxyglutarate (2‑HG) and downstream epigenetic dysregulation and impaired myeloid differentiation. (issa2021acutemyeloidleukemia pages 1-2, fruchtman2024managementofisocitrate pages 1-2)
Recent AML classification systems emphasize molecular genetics. - WHO (2022 revision) generally retains a 20% blast threshold for AML but includes exceptions for some genetically defined AMLs. (shimony2023acutemyeloidleukemia pages 1-2) - ICC (2022) allows genetically defined AML diagnoses at ≥10% blasts for select genetic lesions and introduces an MDS/AML category for 10–19% blasts. (shimony2023acutemyeloidleukemia pages 1-2)
The defining causal factor is somatic gain‑of‑function (“neomorphic”) mutation in IDH1 or IDH2 in leukemic cells. (issa2021acutemyeloidleukemia pages 1-2, fruchtman2024managementofisocitrate pages 1-2)
Hotspot residues / pathogenic variants - IDH1: mutations cluster at R132 (e.g., R132H, R132C, R132L, R132S, R132G). (ivanov2024moleculartargetingof pages 2-4, issa2021acutemyeloidleukemia pages 1-2) - IDH2: mutations cluster at R140 and R172 (notably R140Q and R172K). (ivanov2024moleculartargetingof pages 2-4, fruchtman2024managementofisocitrate pages 1-2)
Frequency in AML - Across reviews, IDH mutations are reported in ~14–20% of AML overall. (fruchtman2024managementofisocitrate pages 1-2) - One treatment‑algorithm review reports an approximate breakdown of ~8% IDH1 and ~12% IDH2 among AML. (issa2021acutemyeloidleukemia pages 1-2)
No IDH‑specific environmental risk factors were identified in the retrieved sources for this run. Epidemiologically, AML overall is strongly age‑associated (median age ~68–70), which indirectly enriches for IDH‑mutated cases because IDH mutations are frequently found in older AML populations. (fruchtman2024managementofisocitrate pages 1-2, kantarjian2024currentstatusand pages 1-2)
No IDH‑specific protective factors were identified in the retrieved sources.
Not identified in retrieved sources for IDH‑mutated AML specifically.
AML commonly presents with symptoms and signs driven by bone‑marrow failure: - Anemia → fatigue, shortness of breath (HPO suggestion: HP:0001903 Anemia, HP:0012378 Fatigue, HP:0002094 Dyspnea). (premnath2023paradigmshiftin pages 1-2, bill2024impactofidh1 pages 1-6) - Neutropenia/immune dysfunction → fever/infection (HPO: HP:0002719 Recurrent infections, HP:0001945 Fever). (premnath2023paradigmshiftin pages 1-2, bill2024impactofidh1 pages 1-6) - Thrombocytopenia → bleeding/petechiae (HPO: HP:0001873 Thrombocytopenia, HP:0000967 Petechiae, HP:0001892 Bleeding). (bill2024impactofidh1 pages 1-6)
A representative case in a 2023 AML review illustrates typical cytopenias and blast burden (Hb 7.5 g/dL, WBC 2.3×10^9/L, platelets 27×10^9/L; 22% marrow myeloblasts). (shimony2023acutemyeloidleukemia pages 1-2)
IDH inhibitors can induce a differentiation syndrome characterized by systemic inflammatory/capillary leak manifestations. In an FDA systematic analysis of relapsed/refractory AML trials, adjudicated differentiation syndrome occurred in 19% of patients treated with ivosidenib and 19% with enasidenib; median onset ~20 and 19 days, respectively; and fatal cases occurred (6% and 5% among DS cases, respectively). (norsworthy2020differentiationsyndromewith pages 3-4)
Clinical manifestations used for case identification include dyspnea, unexplained fever, weight gain, hypotension, acute renal failure, and pulmonary infiltrates/pleuropericardial effusion. (norsworthy2020differentiationsyndromewith pages 3-4)
Phenotype ontology suggestion for DS manifestations: - HP:0002094 Dyspnea, HP:0001945 Fever, HP:0004325 Weight gain, HP:0002615 Hypotension, HP:0001919 Acute kidney injury, HP:0002090 Pneumonia/Pulmonary infiltrates, HP:0000967 Edema.
Transfusion dependence is a major functional burden; IDH‑directed therapy can restore hematopoiesis. In enasidenib‑treated relapsed/refractory IDH2‑mutant AML, 43.1% of RBC transfusion‑dependent patients and 40.2% of platelet transfusion‑dependent patients achieved transfusion independence. (stein2019molecularremissionand pages 1-4)
Hotspots: IDH1 R132; IDH2 R140/R172. (ivanov2024moleculartargetingof pages 2-4, fruchtman2024managementofisocitrate pages 1-2)
Somatic origin is typical for AML; the retrieved sources characterize these as acquired driver mutations in leukemia. (issa2021acutemyeloidleukemia pages 1-2, fruchtman2024managementofisocitrate pages 1-2)
IDH mutational subgroups show distinct co-mutation patterns with clinical implications (e.g., NPM1, DNMT3A, and pathway mutations) and can influence response and resistance. (testa2020isocitratedehydrogenasemutations pages 17-19, lang2023mechanismsofresistance pages 5-7)
A clinically important modifier concept is that IDH2 R140 can behave as a clonal hematopoiesis–like lesion in transplant MRD contexts, with high diagnostic VAF and frequent persistence not necessarily tracking relapse risk. (bill2023impactofidh1andidh2mutationdetection pages 4-5, bill2024impactofidh1 pages 26-30)
IDH mutations promote a hypermethylated state via inhibition of α‑KG–dependent enzymes (TET2 DNA demethylation; histone demethylases), providing a mechanistic basis for epigenetic dysregulation in IDH‑mut AML. (issa2021acutemyeloidleukemia pages 1-2, fruchtman2024managementofisocitrate pages 1-2)
No IDH‑specific environmental contributors were identified in the retrieved sources for this run.
Mutant IDH enzymes lose normal catalytic behavior and acquire neomorphic activity converting α‑ketoglutarate into 2‑hydroxyglutarate (2‑HG). (issa2021acutemyeloidleukemia pages 1-2, fruchtman2024managementofisocitrate pages 1-2)
Accumulated 2‑HG competitively inhibits α‑KG–dependent dioxygenases (including TET2 and histone demethylases), producing DNA/histone hypermethylation and enforcing a myeloid differentiation block that promotes leukemogenesis. (issa2021acutemyeloidleukemia pages 1-2, fruchtman2024managementofisocitrate pages 1-2)
AML often has an acute/subacute presentation due to rapid marrow failure with symptomatic cytopenias. (premnath2023paradigmshiftin pages 1-2)
IDH inhibitor responses can take weeks and reflect differentiation rather than immediate cytotoxicity; in an ivosidenib trial summary the median time to response was ~1.9 months. (fruchtman2024managementofisocitrate pages 3-4)
Diagnosis involves peripheral blood and bone marrow evaluation and includes morphology, immunophenotyping (flow cytometry), cytogenetics, and molecular testing; blast thresholds depend on WHO vs ICC (Section 1). (bill2024impactofidh1 pages 1-6, shimony2023acutemyeloidleukemia pages 1-2)
IHC limitations: A 2024 review notes IDH1 R132H IHC can miss non‑R132H variants and may have ~5–10% false positives, thus molecular testing is often required. (ivanov2024moleculartargetingof pages 2-4)
Evidence supports variant‑specific interpretation of persistent IDH mutations: - In a 2023 HSCT cohort, IDH MRD by ddPCR was common at HSCT (75%); persistence of IDH1 R132 or IDH2 R172 was associated with relapse risk, while persistent IDH2 R140 (often high VAF) was less predictive and may reflect clonal hematopoiesis. (bill2023impactofidh1andidh2mutationdetection pages 4-5, bill2024impactofidh1 pages 26-30) - A 2024 cohort (non‑myeloablative alloHCT with PTCy) found no significant association between persistent IDH mutations pre‑alloHCT and 3‑year outcomes, illustrating current uncertainty and the need for standardized thresholds and variant‑aware interpretation. (ravindra2024persistentidhmutations pages 1-4)
Prognosis in AML is strongly age‑dependent and risk‑stratified by genetics and MRD; older adults historically have poor outcomes even with intensive therapy (e.g., median survival ~9 months and 5‑year survival ≤10% for >60 treated with 7+3 in one 2024 review). (kantarjian2024currentstatusand pages 1-2)
IDH mutation prognostic impact is context‑dependent (co-mutations and variant specifics), and current sources emphasize using broader molecular risk frameworks (e.g., ELN‑style risk) rather than treating IDH mutation alone as a definitive prognostic class. (bill2024impactofidh1 pages 9-13)
IDH1 inhibitors - Ivosidenib: in newly diagnosed IDH1‑mutant AML (subgroup, n=34) a 2024 review reports CR 30.3%, CR/CRh 42.4%, median OS 12.6 months; differentiation syndrome occurred 18% (9% grade ≥3). (fruchtman2024managementofisocitrate pages 4-5)
IDH2 inhibitors - Enasidenib: pivotal phase I/II program in relapsed/refractory IDH2‑mutant AML reported ORR 38.8%, CR 19.6%, median OS 8.8 months; grade 3–4 AEs included hyperbilirubinemia 10%, thrombocytopenia 7%, and differentiation syndrome 6%. (stein2019molecularremissionand pages 1-4)
Ivosidenib + azacitidine (frontline older/unfit; AGILE context) - A health‑economic analysis summarizes that in the randomized AGILE trial, ivosidenib+azacitidine improved event‑free survival (HR 0.33) and overall survival (HR 0.44) vs placebo+azacitidine in newly diagnosed older/unfit IDH1‑mutant AML. (bewersdorf2023costeffectivenessofazacitidine pages 1-2)
Venetoclax + azacitidine (widely used low‑intensity backbone; IDH‑mut subset efficacy) - In pooled phase Ib/III analyses of treatment‑naïve, intensive‑ineligible AML, IDH1/2‑mutant patients had CRc 79% vs 11% (Ven+Aza vs Aza), median OS 24.5 vs 6.2 months, and median duration of remission 29.5 vs 9.5 months. (pollyea2022impactofvenetoclax pages 1-2) - Subgroups: IDH1‑mutant CRc 66.7% (mOS 15.2 months) and IDH2‑mutant CRc 86.0% (mOS not reached). (pollyea2022impactofvenetoclax pages 1-2, pollyea2022impactofvenetoclax pages 5-5)
Adverse events with Ven+Aza in IDH‑mut AML: febrile neutropenia 42.0%, infections 59.3%, pneumonia 27.2%, grade ≥3 AEs 97.5% (in the cited excerpt). (pollyea2022impactofvenetoclax pages 6-7)
A 2024 review outlines DS pathophysiology and management: prompt respiratory support and corticosteroids (dexamethasone 10 mg IV twice daily) with treatment interruption for severe cases. (fruchtman2024managementofisocitrate pages 3-4)
The FDA analysis describes an operational case‑finding algorithm and recommends dexamethasone 10 mg IV q12h until symptoms resolve (≥3 days), plus cytoreduction/supportive measures (hydroxyurea, diuretics, leukapheresis as needed). (norsworthy2020differentiationsyndromewith pages 3-4)
Enasidenib has been studied as post‑alloHCT maintenance; the visual summary of a phase I study indicates no reported differentiation syndrome and provides relapse/survival curves and grade ≥3 AE tables. (fathi2022enasidenibasmaintenance media a35fe258, fathi2022enasidenibasmaintenance media 3bab0af4, fathi2022enasidenibasmaintenance media c85d33dd)
No established primary prevention strategy specific to IDH‑mutated AML was identified in the retrieved sources.
Not established as a naturally occurring veterinary disease entity in retrieved sources; experimental animal models are described below.
Transgenic IDH2R140Q and IDH2R172K zebrafish (often combined with FLT3‑ITD) develop AML‑like disease with differentiation blockade, splenomegaly, transplantability to recipients, and therapeutic response to enasidenib. (wang2023transgenicidh2r172kand pages 1-2, wang2023transgenicidh2r172kand pages 4-7)
Inducible/tissue‑specific IDH2R140Q models cooperate with other lesions to drive acute leukemia and show that deinduction of mutant IDH2 impairs leukemia maintenance. (kats2014protooncogenicroleof pages 1-3)
Human CD34+ HSPC experimental systems show direct differentiation blockade by IDH mutants with inhibitor reversibility (“complete trilineage block of differentiation” reversed by specific inhibitors). (pierangeli2024theleukemicisocitrate pages 1-2)
A 2024 pharmacovigilance analysis using WHO VigiAccess reported 4,072 adverse event reports for enasidenib and ivosidenib combined (2,776 for enasidenib; 1,296 for ivosidenib). Top reported events included off‑label use, death, fatigue, nausea, diarrhea, AML, drug ineffective, differentiation syndrome, and decreased platelet count. (peng2024arealworldstudy pages 1-2, peng2024arealworldstudy pages 4-6)
The following table consolidates high‑yield, evidence‑backed facts (definitions, mechanisms, epidemiology, and treatment outcomes) with DOI URLs:
| Topic | Key finding with quantitative values where available | Source (first author, journal, year) | Publication date (month/year) | PMID | DOI URL |
|---|---|---|---|---|---|
| Definition | IDH-mutated AML is AML with somatic IDH1/IDH2 mutations that generate the oncometabolite 2-HG, causing epigenetic dysregulation and impaired myeloid differentiation; IDH1/2 mutations occur in roughly ~20% of AML overall. (issa2021acutemyeloidleukemia pages 1-2, fruchtman2024managementofisocitrate pages 1-2) | Issa, Blood Cancer Journal, 2021 | 06/2021 | https://doi.org/10.1038/s41408-021-00497-1 | |
| Mutation hotspots | Hotspot substitutions occur almost exclusively at IDH1 R132 and IDH2 R140/R172; common variants include IDH1 R132H/R132C and IDH2 R140Q/R172K. (ivanov2024moleculartargetingof pages 2-4, fruchtman2024managementofisocitrate pages 1-2) | Ivanov, Int J Mol Sci, 2024 | 07/2024 | https://doi.org/10.3390/ijms25137337 | |
| Prevalence in AML | Reviews report IDH mutations in ~14–20% of AML; one treatment algorithm reports ~8% IDH1 and ~12% IDH2. (issa2021acutemyeloidleukemia pages 1-2, fruchtman2024managementofisocitrate pages 1-2) | Fruchtman, Leukemia, 2024 | 04/2024 | https://doi.org/10.1038/s41375-024-02246-2 | |
| Mechanism / pathophysiology | Mutant IDH converts α-ketoglutarate to R-2-hydroxyglutarate, which inhibits α-KG–dependent enzymes including TET2 and JmjC histone demethylases, producing DNA/histone hypermethylation and a differentiation block. (issa2021acutemyeloidleukemia pages 1-2, fruchtman2024managementofisocitrate pages 1-2, cerchione2021idh1idh2inhibitionin pages 1-2) | Cerchione, Front Oncol, 2021 | 03/2021 | https://doi.org/10.3389/fonc.2021.639387 | |
| AML clinical presentation | AML commonly presents with cytopenia-related anemia, infection, and bleeding; an example 2023 review case showed pancytopenia with hemoglobin 7.5 g/dL, WBC 2.3×10^9/L, platelets 27×10^9/L, and 22% marrow myeloblasts. (bill2024impactofidh1 pages 1-6, shimony2023acutemyeloidleukemia pages 1-2) | Shimony, Am J Hematol, 2023 | 01/2023 | https://doi.org/10.1002/ajh.26822 | |
| Classification thresholds (WHO/ICC) | WHO 2022 generally retains ≥20% blasts for AML, with no minimum for some genetically defined AML entities; ICC 2022 allows ≥10% blasts for genetically defined AML (except BCR::ABL1 requiring ≥20%) and introduces an MDS/AML category for 10–19% blasts. (shimony2023acutemyeloidleukemia pages 1-2, shimony2023acutemyeloidleukemia pages 5-6) | Shimony, Am J Hematol, 2023 | 01/2023 | https://doi.org/10.1002/ajh.26822 | |
| Epidemiology / age distribution | AML overall incidence is reported as 4.0 per 100,000; age-adjusted incidence is 18.8 per 100,000 in older adults vs 4.9 per 100,000 in those aged 50–64; median age at diagnosis is ~68 years. (fruchtman2024managementofisocitrate pages 1-2, premnath2023paradigmshiftin pages 1-2) | Fruchtman, Leukemia, 2024 | 04/2024 | https://doi.org/10.1038/s41375-024-02246-2 | |
| Survival statistics | AML 5-year survival improved from 9% in 1980 to 27% in 2017 in one review; another 2023 review reports overall 5-year survival 30.5% for 2012–2018 US cases. (fruchtman2024managementofisocitrate pages 1-2, premnath2023paradigmshiftin pages 1-2) | Premnath, Cancers, 2023 | 05/2023 | https://doi.org/10.3390/cancers15113002 | |
| Older-adult outcomes | Older adults have substantially worse outcomes: one 2024 review states fit patients >60 years treated with intensive 7+3 have median survival ~9 months and 5-year survival ≤10%; before HMA-based therapy, older/unfit patients often had median survival 2–6 months. (kantarjian2024currentstatusand pages 1-2) | Kantarjian, Blood Cancer Journal, 2024 | 09/2024 | https://doi.org/10.1038/s41408-024-01143-2 | |
| Ivosidenib monotherapy (newly diagnosed IDH1-mutant AML) | In newly diagnosed IDH1-mutant AML, ivosidenib monotherapy produced CR 30.3%, CR/CRh 42.4%, median OS 12.6 months; differentiation syndrome occurred in 18% (9% grade ≥3). (fruchtman2024managementofisocitrate pages 4-5) | Fruchtman, Leukemia, 2024 | 04/2024 | https://doi.org/10.1038/s41375-024-02246-2 | |
| Ivosidenib + azacitidine (AGILE context) | In AGILE, ivosidenib + azacitidine significantly improved event-free survival (HR 0.33, 95% CI 0.16–0.69) and overall survival (HR 0.44, 95% CI 0.27–0.73) vs azacitidine alone in newly diagnosed older/ineligible IDH1-mutant AML. (bewersdorf2023costeffectivenessofazacitidine pages 1-2) | Bewersdorf, Leuk Lymphoma, 2023 | 12/2023 | https://doi.org/10.1080/10428194.2022.2140288 | |
| Ivosidenib triplet / early combination data | A phase 1b study of ivosidenib + azacitidine in 23 newly diagnosed patients reported ORR 78.3% and CR 60.9%. (fruchtman2024managementofisocitrate pages 4-5) | Fruchtman, Leukemia, 2024 | 04/2024 | https://doi.org/10.1038/s41375-024-02246-2 | |
| Enasidenib monotherapy (R/R IDH2-mutant AML) | In relapsed/refractory IDH2-mutant AML, enasidenib monotherapy achieved ORR 38.8% (95% CI 32.2–45.7), CR 19.6%, median OS 8.8 months; grade 3–4 treatment-related hyperbilirubinemia 10%, thrombocytopenia 7%, IDH differentiation syndrome 6%. (stein2019molecularremissionand pages 1-4) | Stein, Blood, 2019 | 02/2019 | https://doi.org/10.1182/blood-2018-08-869008 | |
| Pooled outcomes for IDH inhibitors | A 2023 meta-analysis of 1,109 patients reported pooled outcomes for newly diagnosed IDH-mutated AML: CR 47%, ORR 65%, 2-year OS 45%; for R/R disease: CR 21%, ORR 40%, 2-year OS 15%, median OS 8.21 months, median EFS 4.73 months. (chen2023efficacyandsafety pages 6-8) | Chen, Clinical Epigenetics, 2023 | 07/2023 | https://doi.org/10.1186/s13148-023-01529-2 | |
| Differentiation syndrome (FDA systematic analysis) | FDA adjudicated differentiation syndrome in 19% of ivosidenib-treated and 19% of enasidenib-treated R/R AML patients; median onset was 20 days for ivosidenib and 19 days for enasidenib; grade ≥3 reactions occurred in 68% and 66%, and fatal cases in 6% and 5%, respectively. (norsworthy2020differentiationsyndromewith pages 3-4) | Norsworthy, Clin Cancer Res, 2020 | 08/2020 | https://doi.org/10.1158/1078-0432.CCR-20-0834 | |
| MRD / molecular monitoring | Persistent IDH mutations in remission can have prognostic value, but interpretation is variant-specific: IDH1/2 VAF >2.5% at day 30 was associated with short EFS; IDH1/2 VAF <0.2% after induction predicted longer DFS in reported cohorts. (testa2020isocitratedehydrogenasemutations pages 17-19) | Testa, Cancers, 2020 | 08/2020 | https://doi.org/10.3390/cancers12092427 | |
| Post-transplant monitoring | In AML patients undergoing HSCT, diagnostic IDH mutation status did not significantly influence outcomes, but IDH1 R132 and IDH2 R172 positivity at HSCT was associated with inferior outcomes; IDH2 R140 was less informative and may behave more like clonal hematopoiesis. (bill2024impactofidh1 pages 1-6, bill2024impactofidh1 pages 9-13) | Bill, Blood Advances, 2023 | 02/2023 | https://doi.org/10.1182/bloodadvances.2021005789 | |
| Resistance mechanisms | Resistance to IDH inhibitors includes second-site IDH mutations, isoform switching (IDH1↔IDH2), co-occurring RTK/RAS/FLT3 pathway mutations, clonal evolution, and stemness/epigenetic programs; these data support rational combinations such as IDH inhibitor + HMA and IDH inhibitor + venetoclax. (lang2023mechanismsofresistance pages 5-7, issa2021acutemyeloidleukemia pages 5-6, nong2024commondrivermutations pages 8-10) | Lang, Cancers, 2023 | 09/2023 | https://doi.org/10.3390/cancers15184573 | |
| Real-world / implementation note | Enasidenib maintenance after allo-HCT showed survival and safety data in a phase I study, with no cases of differentiation syndrome reported in the visual summary. (fathi2022enasidenibasmaintenance media a35fe258) | Fathi, Blood Advances, 2022 | 11/2022 | https://doi.org/10.1182/bloodadvances.2022008632 |
Table: This table summarizes high-yield, evidence-backed facts for IDH-mutated acute myeloid leukemia, including disease definition, genetics, mechanisms, classification, outcomes, therapies, toxicity, MRD, and epidemiology. It is designed for rapid reuse in a structured disease knowledge base.
References
(issa2021acutemyeloidleukemia pages 1-2): Ghayas C. Issa and Courtney D. DiNardo. Acute myeloid leukemia with idh1 and idh2 mutations: 2021 treatment algorithm. Blood Cancer Journal, Jun 2021. URL: https://doi.org/10.1038/s41408-021-00497-1, doi:10.1038/s41408-021-00497-1. This article has 210 citations and is from a domain leading peer-reviewed journal.
(fruchtman2024managementofisocitrate pages 1-2): Harry Fruchtman, Zachary M. Avigan, Julian A. Waksal, Nicole Brennan, and John O. Mascarenhas. Management of isocitrate dehydrogenase 1/2 mutated acute myeloid leukemia. Leukemia, 38:927-935, Apr 2024. URL: https://doi.org/10.1038/s41375-024-02246-2, doi:10.1038/s41375-024-02246-2. This article has 41 citations and is from a highest quality peer-reviewed journal.
(shimony2023acutemyeloidleukemia pages 1-2): Shai Shimony, Maximilian Stahl, and Richard M. Stone. Acute myeloid leukemia: 2023 update on diagnosis, risk‐stratification, and management. American Journal of Hematology, 98:502-526, Jan 2023. URL: https://doi.org/10.1002/ajh.26822, doi:10.1002/ajh.26822. This article has 524 citations and is from a domain leading peer-reviewed journal.
(ivanov2024moleculartargetingof pages 2-4): Stanislav Ivanov, Olger Nano, Caroline Hana, Amalia Bonano-Rios, and Atif Hussein. Molecular targeting of the isocitrate dehydrogenase pathway and the implications for cancer therapy. International Journal of Molecular Sciences, 25:7337, Jul 2024. URL: https://doi.org/10.3390/ijms25137337, doi:10.3390/ijms25137337. This article has 21 citations.
(norsworthy2020differentiationsyndromewith pages 3-4): Kelly J. Norsworthy, Flora Mulkey, Emma C. Scott, Ashley F. Ward, Donna Przepiorka, Rosane Charlab, Sarah E. Dorff, Albert Deisseroth, Dickran Kazandjian, Rajeshwari Sridhara, Julia A. Beaver, Ann T. Farrell, R. Angelo de Claro, and Richard Pazdur. Differentiation syndrome with ivosidenib and enasidenib treatment in patients with relapsed or refractory idh-mutated aml: a u.s. food and drug administration systematic analysis. Clinical Cancer Research, 26:4280-4288, Aug 2020. URL: https://doi.org/10.1158/1078-0432.ccr-20-0834, doi:10.1158/1078-0432.ccr-20-0834. This article has 115 citations and is from a highest quality peer-reviewed journal.
(wang2023transgenicidh2r172kand pages 1-2): Dandan Wang, Lichuan Zheng, Bowie Yik Ling Cheng, Chun-Fung Sin, Runsheng Li, Sze Pui Tsui, Xinyu Yi, Alvin Chun Hang Ma, Bai Liang He, Anskar Yu Hung Leung, and Xuan Sun. Transgenic idh2r172k and idh2r140q zebrafish models recapitulated features of human acute myeloid leukemia. Oncogene, 42:1272-1281, Feb 2023. URL: https://doi.org/10.1038/s41388-023-02611-y, doi:10.1038/s41388-023-02611-y. This article has 14 citations and is from a domain leading peer-reviewed journal.
(pierangeli2024theleukemicisocitrate pages 1-2): Sara Pierangeli, Serena Donnini, Valerio Ciaurro, Francesca Milano, Valeria Cardinali, Sofia Sciabolacci, Gaetano Cimino, Ilaria Gionfriddo, Roberta Ranieri, Sabrina Cipriani, Eleonora Padiglioni, Roberta Iacucci Ostini, Tiziana Zei, Antonio Pierini, and Maria Paola Martelli. The leukemic isocitrate dehydrogenase (idh) 1/2 mutations impair myeloid and erythroid cell differentiation of primary human hematopoietic stem and progenitor cells (hspcs). Cancers, 16:2675, Jul 2024. URL: https://doi.org/10.3390/cancers16152675, doi:10.3390/cancers16152675. This article has 4 citations.
(peng2024arealworldstudy pages 1-2): Mengmeng Peng, Qian Guo, Zihan Dang, Baiquan Zhang, Manjuan Li, Zixuan Wang, Xuemian Lu, and Jie Lin. A real-world study of adverse drug reactions of two isocitrate dehydrogenase inhibitor based on the us fda adverse event reporting system and vigiaccess databases. Frontiers in Pharmacology, Nov 2024. URL: https://doi.org/10.3389/fphar.2024.1489045, doi:10.3389/fphar.2024.1489045. This article has 3 citations.
(premnath2023paradigmshiftin pages 1-2): Naveen Premnath and Yazan F. Madanat. Paradigm shift in the management of acute myeloid leukemia—approved options in 2023. Cancers, 15:3002, May 2023. URL: https://doi.org/10.3390/cancers15113002, doi:10.3390/cancers15113002. This article has 13 citations.
(kantarjian2024currentstatusand pages 1-2): Hagop Kantarjian, Gautam Borthakur, Naval Daver, Courtney D. DiNardo, Ghayas Issa, Elias Jabbour, Tapan Kadia, Koji Sasaki, Nicholas J. Short, Musa Yilmaz, and Farhad Ravandi. Current status and research directions in acute myeloid leukemia. Blood Cancer Journal, Sep 2024. URL: https://doi.org/10.1038/s41408-024-01143-2, doi:10.1038/s41408-024-01143-2. This article has 113 citations and is from a domain leading peer-reviewed journal.
(bill2024impactofidh1 pages 1-6): M Bill. Impact of idh1 and idh2 mutation detection at diagnosis and in remission in acute myeloid leukemia patients receiving allogeneic transplantation. Unknown journal, 2024.
(stein2019molecularremissionand pages 1-4): Eytan M. Stein, Courtney D. DiNardo, Amir T. Fathi, Daniel A. Pollyea, Richard M. Stone, Jessica K. Altman, Gail J. Roboz, Manish R. Patel, Robert Collins, Ian W. Flinn, Mikkael A. Sekeres, Anthony S. Stein, Hagop M. Kantarjian, Ross L. Levine, Paresh Vyas, Kyle J. MacBeth, Alessandra Tosolini, Jason VanOostendorp, Qiang Xu, Ira Gupta, Thomas Lila, Alberto Risueno, Katharine E. Yen, Bin Wu, Eyal C. Attar, Martin S. Tallman, and Stéphane de Botton. Molecular remission and response patterns in patients with mutant-idh2 acute myeloid leukemia treated with enasidenib. Blood, 133 7:676-687, Feb 2019. URL: https://doi.org/10.1182/blood-2018-08-869008, doi:10.1182/blood-2018-08-869008. This article has 413 citations and is from a highest quality peer-reviewed journal.
(testa2020isocitratedehydrogenasemutations pages 17-19): Ugo Testa, Germana Castelli, and Elvira Pelosi. Isocitrate dehydrogenase mutations in myelodysplastic syndromes and in acute myeloid leukemias. Cancers, 12:2427, Aug 2020. URL: https://doi.org/10.3390/cancers12092427, doi:10.3390/cancers12092427. This article has 27 citations.
(lang2023mechanismsofresistance pages 5-7): Tonio Johannes Lukas Lang, Frederik Damm, Lars Bullinger, and Mareike Frick. Mechanisms of resistance to small molecules in acute myeloid leukemia. Cancers, 15:4573, Sep 2023. URL: https://doi.org/10.3390/cancers15184573, doi:10.3390/cancers15184573. This article has 13 citations.
(bill2023impactofidh1andidh2mutationdetection pages 4-5): Marius Bill, Madlen Jentzsch, Lara Bischof, Jessica Kohlschmidt, Juliane Grimm, Laura Katharina Schmalbrock, Donata Backhaus, Dominic Brauer, Karoline Goldmann, Georg-Nikolaus Franke, Vladan Vucinic, Dietger Niederwieser, Alice S. Mims, Uwe Platzbecker, Ann-Kathrin Eisfeld, and Sebastian Schwind. Impact ofidh1andidh2mutation detection at diagnosis and in remission in patients with aml receiving allogeneic transplantation. Blood Advances, 7:436-444, Feb 2023. URL: https://doi.org/10.1182/bloodadvances.2021005789, doi:10.1182/bloodadvances.2021005789. This article has 42 citations and is from a peer-reviewed journal.
(bill2024impactofidh1 pages 26-30): M Bill. Impact of idh1 and idh2 mutation detection at diagnosis and in remission in acute myeloid leukemia patients receiving allogeneic transplantation. Unknown journal, 2024.
(nong2024commondrivermutations pages 7-8): Tiffany Nong, Shefali Mehra, and Justin Taylor. Common driver mutations in aml: biological impact, clinical considerations, and treatment strategies. Cells, 13:1392, Aug 2024. URL: https://doi.org/10.3390/cells13161392, doi:10.3390/cells13161392. This article has 22 citations.
(wang2023transgenicidh2r172kand pages 4-7): Dandan Wang, Lichuan Zheng, Bowie Yik Ling Cheng, Chun-Fung Sin, Runsheng Li, Sze Pui Tsui, Xinyu Yi, Alvin Chun Hang Ma, Bai Liang He, Anskar Yu Hung Leung, and Xuan Sun. Transgenic idh2r172k and idh2r140q zebrafish models recapitulated features of human acute myeloid leukemia. Oncogene, 42:1272-1281, Feb 2023. URL: https://doi.org/10.1038/s41388-023-02611-y, doi:10.1038/s41388-023-02611-y. This article has 14 citations and is from a domain leading peer-reviewed journal.
(kats2014protooncogenicroleof pages 1-3): Lev M. Kats, Markus Reschke, Riccardo Taulli, Olga Pozdnyakova, Kerri Burgess, Parul Bhargava, Kimberly Straley, Rahul Karnik, Alexander Meissner, Donald Small, Shinsan M. Su, Katharine Yen, Jiangwen Zhang, and Pier Paolo Pandolfi. Proto-oncogenic role of mutant idh2 in leukemia initiation and maintenance. Cell stem cell, 14 3:329-41, Mar 2014. URL: https://doi.org/10.1016/j.stem.2013.12.016, doi:10.1016/j.stem.2013.12.016. This article has 258 citations and is from a highest quality peer-reviewed journal.
(fruchtman2024managementofisocitrate pages 3-4): Harry Fruchtman, Zachary M. Avigan, Julian A. Waksal, Nicole Brennan, and John O. Mascarenhas. Management of isocitrate dehydrogenase 1/2 mutated acute myeloid leukemia. Leukemia, 38:927-935, Apr 2024. URL: https://doi.org/10.1038/s41375-024-02246-2, doi:10.1038/s41375-024-02246-2. This article has 41 citations and is from a highest quality peer-reviewed journal.
(bill2023impactofidh1andidh2mutationdetection pages 1-2): Marius Bill, Madlen Jentzsch, Lara Bischof, Jessica Kohlschmidt, Juliane Grimm, Laura Katharina Schmalbrock, Donata Backhaus, Dominic Brauer, Karoline Goldmann, Georg-Nikolaus Franke, Vladan Vucinic, Dietger Niederwieser, Alice S. Mims, Uwe Platzbecker, Ann-Kathrin Eisfeld, and Sebastian Schwind. Impact ofidh1andidh2mutation detection at diagnosis and in remission in patients with aml receiving allogeneic transplantation. Blood Advances, 7:436-444, Feb 2023. URL: https://doi.org/10.1182/bloodadvances.2021005789, doi:10.1182/bloodadvances.2021005789. This article has 42 citations and is from a peer-reviewed journal.
(ravindra2024persistentidhmutations pages 1-4): Niveditha Ravindra, Laura W. Dillon, Gege Gui, Matthew Smith, Lukasz P. Gondek, Richard J. Jones, Adam Corner, Christopher S. Hourigan, and Alexander J. Ambinder. Persistent idh mutations are not associated with increased relapse or death in patients with idh-mutated acute myeloid leukemia undergoing allogeneic hematopoietic cell transplant with post-transplant cyclophosphamide. Bone Marrow Transplantation, 59:428-430, Jan 2024. URL: https://doi.org/10.1038/s41409-023-02189-9, doi:10.1038/s41409-023-02189-9. This article has 13 citations and is from a peer-reviewed journal.
(bill2024impactofidh1 pages 9-13): M Bill. Impact of idh1 and idh2 mutation detection at diagnosis and in remission in acute myeloid leukemia patients receiving allogeneic transplantation. Unknown journal, 2024.
(fruchtman2024managementofisocitrate pages 4-5): Harry Fruchtman, Zachary M. Avigan, Julian A. Waksal, Nicole Brennan, and John O. Mascarenhas. Management of isocitrate dehydrogenase 1/2 mutated acute myeloid leukemia. Leukemia, 38:927-935, Apr 2024. URL: https://doi.org/10.1038/s41375-024-02246-2, doi:10.1038/s41375-024-02246-2. This article has 41 citations and is from a highest quality peer-reviewed journal.
(bewersdorf2023costeffectivenessofazacitidine pages 1-2): Jan Philipp Bewersdorf, Kishan K. Patel, George Goshua, Rory M. Shallis, Nikolai A. Podoltsev, Maximilian Stahl, Eytan M. Stein, Scott F. Huntington, and Amer M. Zeidan. Cost-effectiveness of azacitidine and ivosidenib in newly diagnosed older, intensive chemotherapy-ineligible patients with idh1 -mutant acute myeloid leukemia. Leukemia & Lymphoma, 64:454-461, Dec 2023. URL: https://doi.org/10.1080/10428194.2022.2140288, doi:10.1080/10428194.2022.2140288. This article has 9 citations and is from a peer-reviewed journal.
(pollyea2022impactofvenetoclax pages 1-2): Daniel A. Pollyea, Courtney D. DiNardo, Martha L. Arellano, Arnaud Pigneux, Walter Fiedler, Marina Konopleva, David A. Rizzieri, B. Douglas Smith, Atsushi Shinagawa, Roberto M. Lemoli, Monique Dail, Yinghui Duan, Brenda Chyla, Jalaja Potluri, Catherine L. Miller, and Hagop M. Kantarjian. Impact of venetoclax and azacitidine in treatment-naïve patients with acute myeloid leukemia and idh1/2 mutations. Clinical Cancer Research, 28:2753-2761, Jan 2022. URL: https://doi.org/10.1158/1078-0432.ccr-21-3467, doi:10.1158/1078-0432.ccr-21-3467. This article has 194 citations and is from a highest quality peer-reviewed journal.
(pollyea2022impactofvenetoclax pages 5-5): Daniel A. Pollyea, Courtney D. DiNardo, Martha L. Arellano, Arnaud Pigneux, Walter Fiedler, Marina Konopleva, David A. Rizzieri, B. Douglas Smith, Atsushi Shinagawa, Roberto M. Lemoli, Monique Dail, Yinghui Duan, Brenda Chyla, Jalaja Potluri, Catherine L. Miller, and Hagop M. Kantarjian. Impact of venetoclax and azacitidine in treatment-naïve patients with acute myeloid leukemia and idh1/2 mutations. Clinical Cancer Research, 28:2753-2761, Jan 2022. URL: https://doi.org/10.1158/1078-0432.ccr-21-3467, doi:10.1158/1078-0432.ccr-21-3467. This article has 194 citations and is from a highest quality peer-reviewed journal.
(pollyea2022impactofvenetoclax pages 6-7): Daniel A. Pollyea, Courtney D. DiNardo, Martha L. Arellano, Arnaud Pigneux, Walter Fiedler, Marina Konopleva, David A. Rizzieri, B. Douglas Smith, Atsushi Shinagawa, Roberto M. Lemoli, Monique Dail, Yinghui Duan, Brenda Chyla, Jalaja Potluri, Catherine L. Miller, and Hagop M. Kantarjian. Impact of venetoclax and azacitidine in treatment-naïve patients with acute myeloid leukemia and idh1/2 mutations. Clinical Cancer Research, 28:2753-2761, Jan 2022. URL: https://doi.org/10.1158/1078-0432.ccr-21-3467, doi:10.1158/1078-0432.ccr-21-3467. This article has 194 citations and is from a highest quality peer-reviewed journal.
(fathi2022enasidenibasmaintenance media a35fe258): Amir T. Fathi, Haesook T. Kim, Robert J. Soiffer, Mark J. Levis, Shuli Li, Annette S. Kim, Alice S. Mims, Zachariah DeFilipp, Areej El-Jawahri, Steven L. McAfee, Andrew M. Brunner, Rupa Narayan, Laura W. Knight, Devon Kelley, AJ S. Bottoms, Lindsey H. Perry, Jonathan L. Wahl, Jennifer Brock, Elayne Breton, Vincent T. Ho, and Yi-Bin Chen. Enasidenib as maintenance following allogeneic hematopoietic cell transplantation for idh2-mutated myeloid malignancies. Blood Advances, 6:5857-5865, Nov 2022. URL: https://doi.org/10.1182/bloodadvances.2022008632, doi:10.1182/bloodadvances.2022008632. This article has 64 citations and is from a peer-reviewed journal.
(fathi2022enasidenibasmaintenance media 3bab0af4): Amir T. Fathi, Haesook T. Kim, Robert J. Soiffer, Mark J. Levis, Shuli Li, Annette S. Kim, Alice S. Mims, Zachariah DeFilipp, Areej El-Jawahri, Steven L. McAfee, Andrew M. Brunner, Rupa Narayan, Laura W. Knight, Devon Kelley, AJ S. Bottoms, Lindsey H. Perry, Jonathan L. Wahl, Jennifer Brock, Elayne Breton, Vincent T. Ho, and Yi-Bin Chen. Enasidenib as maintenance following allogeneic hematopoietic cell transplantation for idh2-mutated myeloid malignancies. Blood Advances, 6:5857-5865, Nov 2022. URL: https://doi.org/10.1182/bloodadvances.2022008632, doi:10.1182/bloodadvances.2022008632. This article has 64 citations and is from a peer-reviewed journal.
(fathi2022enasidenibasmaintenance media c85d33dd): Amir T. Fathi, Haesook T. Kim, Robert J. Soiffer, Mark J. Levis, Shuli Li, Annette S. Kim, Alice S. Mims, Zachariah DeFilipp, Areej El-Jawahri, Steven L. McAfee, Andrew M. Brunner, Rupa Narayan, Laura W. Knight, Devon Kelley, AJ S. Bottoms, Lindsey H. Perry, Jonathan L. Wahl, Jennifer Brock, Elayne Breton, Vincent T. Ho, and Yi-Bin Chen. Enasidenib as maintenance following allogeneic hematopoietic cell transplantation for idh2-mutated myeloid malignancies. Blood Advances, 6:5857-5865, Nov 2022. URL: https://doi.org/10.1182/bloodadvances.2022008632, doi:10.1182/bloodadvances.2022008632. This article has 64 citations and is from a peer-reviewed journal.
(NCT03839771 chunk 1): A Study of Ivosidenib or Enasidenib in Combination With Induction Therapy and Consolidation Therapy, Followed by Maintenance Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myedysplastic Syndrome EB2, With an IDH1 or IDH2 Mutation, Respectively, Eligible for Intensive Chemotherapy. Stichting Hemato-Oncologie voor Volwassenen Nederland. 2019. ClinicalTrials.gov Identifier: NCT03839771
(NCT06387069 chunk 1): A Study to Evaluate HMPL-306 in Patients With IDH1or IDH2-mutated Acute Myeloid Leukemia. Hutchmed. 2024. ClinicalTrials.gov Identifier: NCT06387069
(NCT04603001 chunk 1): Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations. Eli Lilly and Company. 2020. ClinicalTrials.gov Identifier: NCT04603001
(NCT05401097 chunk 1): Alice Mims. IDH Targeted/Non- Targeted vs Non-targeted/IDH-targeted Approaches in the Treatment of Newly Diagnosed IDH Mutated AML Patients Not Candidates for Intensive Induction Therapy (I- DATA Study). Alice Mims. 2022. ClinicalTrials.gov Identifier: NCT05401097
(peng2024arealworldstudy pages 4-6): Mengmeng Peng, Qian Guo, Zihan Dang, Baiquan Zhang, Manjuan Li, Zixuan Wang, Xuemian Lu, and Jie Lin. A real-world study of adverse drug reactions of two isocitrate dehydrogenase inhibitor based on the us fda adverse event reporting system and vigiaccess databases. Frontiers in Pharmacology, Nov 2024. URL: https://doi.org/10.3389/fphar.2024.1489045, doi:10.3389/fphar.2024.1489045. This article has 3 citations.
(cerchione2021idh1idh2inhibitionin pages 1-2): Claudio Cerchione, Alessandra Romano, Naval Daver, Courtney DiNardo, Elias Joseph Jabbour, Marina Konopleva, Farhad Ravandi-Kashani, Tapan Kadia, Maria Paola Martelli, Alessandro Isidori, Giovanni Martinelli, and Hagop Kantarjian. Idh1/idh2 inhibition in acute myeloid leukemia. Frontiers in Oncology, Mar 2021. URL: https://doi.org/10.3389/fonc.2021.639387, doi:10.3389/fonc.2021.639387. This article has 85 citations.
(shimony2023acutemyeloidleukemia pages 5-6): Shai Shimony, Maximilian Stahl, and Richard M. Stone. Acute myeloid leukemia: 2023 update on diagnosis, risk‐stratification, and management. American Journal of Hematology, 98:502-526, Jan 2023. URL: https://doi.org/10.1002/ajh.26822, doi:10.1002/ajh.26822. This article has 524 citations and is from a domain leading peer-reviewed journal.
(chen2023efficacyandsafety pages 6-8): Xiu Chen, Hongyun Xing, Xiaolu Xie, Liqiu Kou, Jun Li, and Yaling Li. Efficacy and safety of fda-approved idh inhibitors in the treatment of idh mutated acute myeloid leukemia: a systematic review and meta-analysis. Clinical Epigenetics, Jul 2023. URL: https://doi.org/10.1186/s13148-023-01529-2, doi:10.1186/s13148-023-01529-2. This article has 30 citations and is from a peer-reviewed journal.
(issa2021acutemyeloidleukemia pages 5-6): Ghayas C. Issa and Courtney D. DiNardo. Acute myeloid leukemia with idh1 and idh2 mutations: 2021 treatment algorithm. Blood Cancer Journal, Jun 2021. URL: https://doi.org/10.1038/s41408-021-00497-1, doi:10.1038/s41408-021-00497-1. This article has 210 citations and is from a domain leading peer-reviewed journal.
(nong2024commondrivermutations pages 8-10): Tiffany Nong, Shefali Mehra, and Justin Taylor. Common driver mutations in aml: biological impact, clinical considerations, and treatment strategies. Cells, 13:1392, Aug 2024. URL: https://doi.org/10.3390/cells13161392, doi:10.3390/cells13161392. This article has 22 citations.