Galanello R, Stamatoyannopoulos G, Papayannopoulou T
Department of Medicine, University of Washington, Seattle 98195.
J Clin Invest. 1988 Apr;81(4):1209-16. doi: 10.1172/JCI113437.
The in vitro effect of S-stage-specific drugs on the fetal hemoglobin (Hb F) potential of erythroid precursors and progenitors was tested by exposing bone marrow cells to 5-aza-2'-deoxycytidine, Ara-C, or hydroxyurea in suspension cultures and reculturing the cells in drug-free clonal cultures. Analysis of Hb F in the erythroblasts present at the end of suspension cultures and in the erythroid colonies formed from treated progenitors showed that 1 X 10(-9)-5 X 10(-8) M 5-aza-2'-deoxycytidine produced a concentration-related increase in the proportion of Hb F-positive erythroblasts, of Hb F-positive erythroid CFU (CFUe) colonies, and at the higher doses used, an increased Hb F expression in erythroid burst-forming unit (BFUe)-derived colonies. Preincubation of bone marrow cells with Ara-C produced significant megaloblastic changes by the end of the 2-d incubation and increased the proportion of Hb F-positive erythroblasts, CFUe colonies, and e-clusters, but BFUe-derived progeny was unaffected. Hydroxyurea failed to produce significant changes in Hb F at the range of concentrations used. The data raise the possibility of more than one mechanism underlying the stimulation of Hb F by S-stage drugs.
通过将骨髓细胞悬浮培养于5-氮杂-2'-脱氧胞苷、阿糖胞苷或羟基脲中，并在无药物的克隆培养中对细胞进行再培养，测试了S期特异性药物对红系前体细胞和祖细胞胎儿血红蛋白（Hb F）潜力的体外效应。对悬浮培养结束时存在的幼红细胞以及由处理后的祖细胞形成的红系集落中的Hb F进行分析，结果显示，1×10⁻⁹ - 5×10⁻⁸ M的5-氮杂-2'-脱氧胞苷使Hb F阳性幼红细胞、Hb F阳性红系集落形成单位（CFUe）集落的比例呈浓度依赖性增加，并且在使用的较高剂量下，红系爆式集落形成单位（BFUe）衍生集落中的Hb F表达增加。在2天培养结束时，用阿糖胞苷预孵育骨髓细胞会产生明显的巨幼样改变，并增加Hb F阳性幼红细胞、CFUe集落和e簇的比例，但BFUe衍生的后代未受影响。在所使用的浓度范围内，羟基脲未能使Hb F产生显著变化。这些数据增加了S期药物刺激Hb F存在多种机制的可能性。
