Technical University of Munich, Munich, Germany.
Ann N Y Acad Sci. 2014 Mar;1310(1):7-31. doi: 10.1111/nyas.12362. Epub 2014 Feb 4.
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.
造血干细胞（HSCs）是一种独特的体干细胞群体，既能自我更新以长期重建 HSCs，又能分化为造血祖细胞（HPCs），这些祖细胞又以层级方式产生整个骨髓和淋巴谱系。这些谱系的分化和成熟发生在骨髓（BM）龛位中，这个微环境调节自我更新、存活、分化和增殖，需要 HSCs 中的信号通路之间的相互作用和龛位来建立和维持体内平衡。部分分化的骨髓谱系细胞内遗传突变和细胞遗传学异常的积累，特别是由于暴露于苯或细胞毒性抗癌药物，可导致急性髓系白血病和骨髓增生异常综合征等恶性肿瘤的发生。更好地了解驱动这些恶性肿瘤和易感性因素的机制，无论是在 HPCs 内还是在 BM 龛位内的细胞中，可能会导致开发预防职业和癌症治疗诱导疾病的策略。
