The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment.
Detection, treatment, and prevention of bone marrow diseases have long been the aims of experimental and clinical hematologists and mechanistically oriented toxicologists. Among these diseases is aplastic anemia, which manifests as the cessation of normal blood cell production; the leukemias, in contrast, feature the production of excessive hematologic cancer cells. Both diseases are associated with exposure to either industrial chemicals or cancer chemotherapeutic agents. Studies of hematopoietic bone marrow cells in culture have shown that the generation of circulating blood cells requires the interaction of hematopoietic stem cells (HSCs) with supporting marrow stromal cells; yet, isolation of HSCs from bone destroys the unique morphology of the marrow stroma in which the HSCs reside. Imaging techniques and related studies have made it possible to examine specific niches where HSCs may either initiate differentiation toward mature blood cells or reside in a dormant state awaiting a signal to begin differentiation. HSCs and related cells may be highly vulnerable to the mutagenic or toxic effects of drugs or other chemicals early in these processes. Additional studies are required to determine the mechanisms by which drug or chemical exposure may affect these cells and lead to either depression of bone marrow function or to leukemia.
Ernest Mario School of Pharmacy, The State University of New Jersey, Piscataway, New Jersey; The Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Robert
R
Snyder
D000818:Animals; D001554:Benzene / Q000633:toxicity; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000266:history / Q000473:pathology; D004781:Environmental Exposure / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology*; D049673:History, 20th Century; D006801:Humans; D019995:Laboratory Chemicals / Q000633:toxicity*; D007938:Leukemia / Q000209:etiology* / Q000266:history / Q000473:pathology; D055153:Stem Cell Niche / Q000187:drug effects / Q000502:physiology*
D019995:Laboratory Chemicals; D001554:Benzene
benzene; bone marrow niche; leukemia; stem cells