Zaker F, Darley R L, al Sabah A, Burnett A K
Department of Haematology, University of Wales College of Medicine, Cardiff, U.K.
Leuk Res. 1997 Jul;21(7):635-40. doi: 10.1016/s0145-2126(97)00022-2.
RAS mutations occur frequently in acute myeloid leukaemia and myelodysplasia, suggesting a functional role for this oncogene in leukaemogenesis. We show here, for the first time, that both N-RAS and H-RAS can impair erythroid differentiation of erythroleukaemia cells induced with hexamethylene bisacetamide. Transformation by RAS allowed extended proliferation in the presence of inducer and also inhibited maturation as measured by impaired haemoglobinization and reduction in cell size. These data provide an interesting counterpoint to the effect of mutant RAS on monocytic cells, where it has a potentiating effect on differentiation and may indicate a causal link between the activation of RAS and erythroid lineage dysplasia in preleukaemia.
RAS突变在急性髓系白血病和骨髓增生异常综合征中频繁发生,提示该癌基因在白血病发生过程中发挥功能性作用。我们在此首次表明,N-RAS和H-RAS均可损害由六亚甲基双乙酰胺诱导的红白血病细胞的红系分化。RAS介导的转化使得细胞在诱导剂存在的情况下能够持续增殖,并且还通过血红蛋白化受损和细胞大小减小来抑制细胞成熟。这些数据为突变型RAS对单核细胞的影响提供了一个有趣的对比,在单核细胞中,突变型RAS对分化具有促进作用,这可能表明RAS激活与白血病前期红系发育异常之间存在因果关系。