The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment.
Hematopoietic stem cells (HSCs) are a unique population of somatic stem cells that can both self-renew for long-term reconstitution of HSCs and differentiate into hematopoietic progenitor cells (HPCs), which in turn give rise, in a hierarchical manner, to the entire myeloid and lymphoid lineages. The differentiation and maturation of these lineages occurs in the bone marrow (BM) niche, a microenvironment that regulates self-renewal, survival, differentiation, and proliferation, with interactions among signaling pathways in the HSCs and the niche required to establish and maintain homeostasis. The accumulation of genetic mutations and cytogenetic abnormalities within cells of the partially differentiated myeloid lineage, particularly as a result of exposure to benzene or cytotoxic anticancer drugs, can give rise to malignancies like acute myeloid leukemia and myelodysplastic syndrome. Better understanding of the mechanisms driving these malignancies and susceptibility factors, both within HPCs and cells within the BM niche, may lead to the development of strategies for prevention of occupational and cancer therapy-induced disease.
Technical University of Munich, Munich, Germany.
Helmut
H
Greim
Debra A
DA
Kaden
Richard A
RA
Larson
Christine M
CM
Palermo
Jerry M
JM
Rice
David
D
Ross
Robert
R
Snyder
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D004781:Environmental Exposure / Q000009:adverse effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019995:Laboratory Chemicals / Q000633:toxicity*; D007938:Leukemia / Q000209:etiology*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D055153:Stem Cell Niche / Q000187:drug effects / Q000502:physiology*
D019995:Laboratory Chemicals
benzene; bone marrow niche; chemotherapeutic alkylating agents; leukemia; myelodysplastic syndrome; stem cells; topoisomerase II