Irons R D, Stillman W S
Molecular Toxicology and Environmental Health Sciences Program, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262.
Stem Cells. 1993 May;11(3):235-42. doi: 10.1002/stem.5530110311.
In tissues such as bone marrow with normally high rates of cell division, proliferation is tightly coordinated with cell differentiation. Survival, proliferation and differentiation of early hematopoietic progenitor cells depend on the growth factors, interleukin 3 (IL-3) and/or granulocyte-macrophage colony stimulating factor (GM-CSF) and their synergism with other cytokines. We provide evidence that a characteristic shared by a diverse group of compounds with demonstrated leukemogenic potential is the ability to act synergistically with GM-CSF. This results in an increase in recruitment of a resting population of hematopoietic progenitor cells normally unresponsive to the cytokine and a twofold increase in the size of the proliferating cell population normally regarded to be at risk of transformation in leukemogenesis. These findings support the possibility that transient alterations in hematopoietic progenitor cell differentiation may be an important factor in the early stages of development of leukemia secondary to chemical or drug exposure.
在诸如骨髓这种正常细胞分裂率较高的组织中，增殖与细胞分化紧密协调。早期造血祖细胞的存活、增殖和分化依赖于生长因子、白细胞介素3（IL-3）和/或粒细胞-巨噬细胞集落刺激因子（GM-CSF）以及它们与其他细胞因子的协同作用。我们提供的证据表明，一组具有白血病生成潜力的不同化合物共有的一个特征是能够与GM-CSF协同作用。这导致原本对该细胞因子无反应的静止造血祖细胞群体的募集增加，以及通常被认为在白血病发生过程中有转化风险的增殖细胞群体大小增加两倍。这些发现支持了这样一种可能性，即造血祖细胞分化的短暂改变可能是化学或药物暴露继发白血病早期发展的一个重要因素。
