This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "myelosuppression#Multilineage Peripheral Cytopenias"). Conforming nodes should substitute the disorder-specific cytotoxic driver (the particular antineoplastic agent or radiation exposure) and may specialize the cytopenia node to a predominant lineage (e.g. irinotecan/neutropenia-predominant, carboplatin/ thrombocytopenia-predominant) while preserving the conserved HSPC-injury → marrow-suppression → cytopenia → complication chain. The key conformance / consequence target is "myelosuppression#Multilineage Peripheral Cytopenias".
Vascularized human bone-marrow-on-chip myelotoxicity model
ORGAN_ON_CHIP
namo:OrganOnChip
Two-channel human bone-marrow microphysiological system that co-cultures CD34+ hematopoietic cells with bone-marrow-derived stromal cells in a fibrin gel beside a perfused, endothelium-lined vascular channel. The system supports multilineage myeloerythroid development and reproduces marrow injury and recovery after clinically relevant chemotherapeutic-drug and ionizing-radiation exposures.
clinically relevant chemotherapeutic-drug exposure
ionizing-radiation exposure
drug-induced myelosuppression and marrow recovery
hematopoietic progenitor cell
CL:0008001
Cell Ontology (CL)
Relation: this experimental model uses this cell type
This experimental model uses hematopoietic progenitor cell, annotated with hematopoietic precursor cell (CL:0008001). CL:0008001 is a cell type from the Cell Ontology.
Organism
human
NCBITaxon:9606
NCBI Taxonomy (NCBITaxon)
Relation: this experimental model is built in this organism
This experimental model is built in human, annotated with Homo sapiens (NCBITaxon:9606). NCBITaxon:9606 is an organism from the NCBI Taxonomy.
Tissue
bone marrow
UBERON:0002371
Uberon multi-species anatomy ontology (UBERON)
Relation: this experimental model uses this anatomical location
This experimental model uses bone marrow (UBERON:0002371). UBERON:0002371 is an anatomical location from the Uberon multi-species anatomy ontology.
Cell source
Human CD34+ cells co-cultured with bone-marrow-derived stromal cells; the parallel vascular channel is lined by human vascular endothelium.
Culture
Vascularized two-channel microfluidic bone-marrow chip with a fibrin-gel hematopoietic compartment and a continuously perfused endothelial channel.
Pathograph links
Bone Marrow Hematopoietic Suppression
The chip recapitulates marrow injury and subsequent recovery after drug-induced myelosuppression, directly modeling suppression and restoration of hematopoietic output.
Scope is limited to the two marrow-level mechanisms directly demonstrated in the publication. The model is not linked to peripheral cytopenias or their clinical complications because those downstream outcomes were not measured on chip.
Evidence: 1
Cytotoxic Insult to Proliferating Hematopoietic Progenitors
trigger
The conserved initiating lesion is cytotoxic damage to the rapidly dividing hematopoietic stem and progenitor cells (HSPCs) of the bone marrow. Because antiproliferative chemotherapy and radiation are not selective for tumor cells, the highly proliferative marrow compartment is collaterally injured, triggering progenitor apoptosis and cell-cycle arrest regardless of the specific agent involved.
Downstream
-
Bone Marrow Hematopoietic Suppression
Progenitor injury and apoptosis reduce the marrow's capacity to sustain hematopoiesis.
Show evidence (3 references)
"Proliferating hematopoietic stem and progenitor cells (HSPCs) in the bone marrow are particularly susceptible to chemotherapy-induced damage."
Establishes the conserved initiating lesion of this module — that proliferating marrow HSPCs are the cells preferentially injured by cytotoxic chemotherapy. Evidence source is OTHER because this is a review article.
"Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HPSCs) often results in myelosuppression that adversely affects patient health and quality of life"
Directly links HSPC damage to myelosuppression as the downstream consequence captured by this module. Evidence source is OTHER because this is a review article.
"trilaciclib transiently maintains HSPC in G1 arrest and protects them from chemotherapy damage, leading to faster hematopoietic recovery and enhanced antitumor immunity"
Preclinical (animal-model) evidence that holding HSPCs out of cycle protects them from chemotherapy, confirming that the proliferative state of progenitors is what makes them vulnerable — the mechanistic basis of this trigger node.
Bone Marrow Hematopoietic Suppression
central effector
Loss of functional progenitors and acute injury to marrow cellularity and the supporting vascular niche suppress hematopoietic output. This is the central effector step: the marrow can no longer replace circulating blood cells at the normal rate, and the deficit becomes the dose-limiting toxicity of the cytotoxic regimen.
Downstream
-
Multilineage Peripheral Cytopenias
Reduced marrow output lowers the numbers of mature blood cells released to the periphery across multiple lineages.
Show evidence (2 references)
"The resultant bone marrow suppression is a major dose-limiting side effect."
Identifies marrow suppression as the dose-limiting consequence of chemotherapy-induced hematopoietic toxicity, the central effector step of this module. Evidence source is MODEL_ORGANISM because the mechanism is established in a mouse 5-fluorouracil study.
"A single injection of 5-FU did not alter mouse bone structure but caused acute damage to bone marrow cellularity and vasculature."
Shows that a representative cytotoxic agent acutely damages marrow cellularity and the vascular niche, the injury that suppresses hematopoietic output. Evidence source is MODEL_ORGANISM (mouse model).
Multilineage Peripheral Cytopenias
effector
Suppressed marrow output reduces the mature blood cells reaching the circulation, producing the multilineage cytopenias that define myelosuppression: neutropenia, anemia, and thrombocytopenia (with lymphopenia in some regimens). This is the key conformance target of the module; conforming disorder nodes may specialize it to the lineage that predominates for a given agent.
Downstream
-
Cytopenia-Related Clinical Complications
Each cytopenia drives its characteristic clinical complication.
Show evidence (3 references)
"one of the most common side effects of chemotherapy is myelosuppression, which typically manifests as neutropenia, anemia, thrombocytopenia, and/or lymphopenia"
Directly enumerates the multilineage cytopenias that constitute this effector node. Evidence source is OTHER because this is a review article.
"Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HSPC) causes multi-lineage myelosuppression."
A human clinical trial frames chemotherapy-induced HSPC damage as the cause of multilineage myelosuppression, supporting the convergence onto this effector node.
"anemia (decreased red blood cells) and thrombocytopenia (decreased platelets)"
Decomposes myelosuppression into peripheral cytopenias mapped to their cell lineages (red cells, platelets). Evidence source is OTHER because this is a review article.