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Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Deep Research Fallback

⚠️ Fallback MONDO:0004967

Acute Lymphoblastic Leukemia Deep Research Fallback

Provider Attempts

  • 2026-05-08T13:00Z: just research-disorder asta Acute_Lymphoblastic_Leukemia failed: agentapi not found in PATH and no provider API keys configured (OPENAI_API_KEY, EDISON_API_KEY, ASTA_API_KEY, PERPLEXITY_API_KEY all unset in this environment).
  • 2026-05-08T13:00Z: just research-disorder openai Acute_Lymphoblastic_Leukemia failed for the same reason.
  • 2026-05-08T13:00Z: just research-disorder perplexity Acute_Lymphoblastic_Leukemia failed for the same reason.
  • 2026-05-08T13:00Z: just research-disorder falcon Acute_Lymphoblastic_Leukemia failed for the same reason.

No provider-generated research artifact was available to integrate. Curation therefore proceeded from previously fetched PubMed abstracts and full-text caches in references_cache/, without hand-editing any cache files.

Evidence Scope Used For Curation

  • PMID:23523389 (Inaba H, Greaves M, Mullighan CG. Lancet 2013) — comprehensive Lancet Seminar review on ALL biology, genetics, treatment, and outcomes. Used to anchor:
  • founding-lesion model (genome-wide profiling, recurrent translocations and aneuploidy)
  • prenatal/in-utero initiation language for the "Acquisition of Initiating Genetic Lesion" pathophysiology node
  • differentiation block (PAX5, IKZF1, EBF1 alterations in >2/3 of B-ALL)
  • bone marrow failure (induction therapy "restores normal haematopoiesis")
  • Ph-like / BCR-ABL1-like ALL subtype definition (10-12% of B-ALL, BCR-ABL1-negative, IKZF1-altered, poor outcome)
  • PMID:15472075 (Weng AP et al. Science 2004) — the landmark NOTCH1 paper, used to anchor activating NOTCH1 mutations as the dominant driver in T-ALL (>50% of cases).
  • PMID:19129520 (Mullighan CG et al. NEJM 2009) — IKZF1 deletion as an independent predictor of poor outcome in B-cell ALL.
  • PMID:41251904 (recent Ph+ ALL review) — used to anchor the BCR-ABL1 fusion defining the Ph+ ALL subtype.

Curation Conclusions

The accepted disease model for ALL is a multi-step transformation in which a founding cytogenetic lesion (translocation creating a chimeric oncogene or aneuploidy) is acquired in a B- or T-lymphoid progenitor — often in utero in B-ALL — followed by acquisition of cooperating mutations that: - corrupt lymphoid transcriptional programs (chimeric TFs; KMT2A-driven HOXA upregulation; NOTCH1 in T-ALL) - block differentiation (IKZF1, PAX5, EBF1 lesions in B-ALL; CDKN2A/B loss most prominent in T-ALL) - drive constitutive proliferation/survival signaling (BCR-ABL1 RAS/PI3K/JAK, NOTCH1-MYC, KMT2A-HOXA9/MEIS1)

The clonal lymphoblast population then expands in the marrow and disseminates to extramedullary sites, producing two dominant clinical axes: 1. Bone marrow failure with pancytopenia (anemia, bleeding from thrombocytopenia, infections from neutropenia) 2. Extramedullary disease (lymphadenopathy, hepatosplenomegaly, anterior mediastinal mass in T-ALL, CNS infiltration as a sanctuary site).

Risk stratification, treatment choice (TKIs in Ph+ and Ph-like ALL, JAK inhibitors in CRLF2-rearranged disease, blinatumomab/inotuzumab/CAR-T in relapsed B-ALL, allogeneic HSCT for highest-risk groups), and prognosis are governed largely by molecular subtype and MRD response.

Subtypes

Curated subtypes in the YAML: - B-ALL with ETV6-RUNX1 (favorable) - B-ALL with TCF3-PBX1 (intermediate, historical CNS relapse risk) - B-ALL with KMT2A rearrangement (high-risk; infant-predominant) - Ph+ ALL (BCR-ABL1) (TKI-targetable) - Ph-like ALL (BCR-ABL1-like) (high-risk; kinase-rearranged; partly TKI/JAK-targetable) - T-ALL (NOTCH1-driven; mediastinal mass; ETP-ALL subset)

Items Intentionally Skipped

  • icdo_morphology was left as the broad "Leukemia" classification because splitting into subtype-specific codes (e.g., 9811/3 B-ALL NOS, 9837/3 T-ALL) on a parent disorder would require either duplicating the parent or moving the field per subtype. Worth revisiting if ICDO subtyping at the subtype level is later added to the schema.
  • Each fusion genetic entry was given a single canonical gene_term (the more clinically central partner: ABL1 for BCR-ABL1, RUNX1 for ETV6-RUNX1, PBX1 for TCF3-PBX1). The gene_term slot is single-valued, so the second partner is documented inline in notes with its hgnc: ID for traceability.