The bone marrow niche, stem cells, and leukemia: Impact of drugs, chemicals, and the environment

Helmut Greim, Debra A. Kaden, Richard A. Larson, Christine M. Palermo, Jerry M. Rice, David Ross, Robert Snyder

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)7-31
Number of pages25
JournalAnnals of the New York Academy of Sciences
Volume1310
Issue number1
DOIs
StatePublished - Mar 2014
Externally publishedYes

Keywords

  • Benzene
  • Bone marrow niche
  • Chemotherapeutic alkylating agents
  • Leukemia
  • Myelodysplastic syndrome
  • Stem cells
  • Topoisomerase II

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