Receptor and nonreceptor protein tyrosine kinases (PTKs) play a key role in the control of normal and neoplastic cell growth. The availability of PTK inhibitors prompted us to evaluate the effects of genistein, a natural inhibitor of PTKs, on in vitro colony formation by normal multilineage colony-forming units (CFU-Mix), erythroid bursts (BFU-E), granulocyte-macrophage colony-forming units (CFU-GM), long-term culture-initiating cells (LTC-IC) and acute myelogenous leukaemia colony-forming units (CFU-AML).Continuous exposure of normal marrow and blood mononuclear non-adherent cells, blood CD34+CD45RA- cells, and leukaemic blasts to increasing doses of genistein (1-100 microM) resulted in a statistically significant (P < or = 0.05) dose-dependent suppression of CFU-Mix, BFU-E, CFU-GM and CFU-AML growth. Regression analysis showed that growth inhibition was linearly related to genistein concentration. Genistein dose causing 50% inhibition (ID50) of CFU-AML was significantly lower compared to CFU-GM ID50 for marrow (19 v 32 microM, P < or = 0.017), unseparated blood (19 v 44 microM, P < or = 0.028) or CD34+CD45RA- blood (19 v 36, P < or = 0.04).Preincubation of leukaemic blasts with genistein (200 microM) for 1-2h confirmed that CFU-AML were significantly more sensitive than normal marrow and blood CFU-GM to genistein. Preincubation conditions which maximally suppressed leukaemic and normal colony growth spared a substantial percentage of marrow (29 +/- 4%) and blood (40 +/- 3%) LTC-IC. In conclusion, our data demonstrate that: (a) genistein strongly inhibits the growth of normal and leukaemic haemopoietic progenitors;(b) growth inhibition is dose- and time-dependent; (c) leukaemic progenitors are more sensitive than normal progenitors to genistein-induced growth inhibition; (d) genistein exerts a direct toxic effect on haemopoietic cells while sparing a substantial proportion of LTC-IC. The potent CFU-AML growth inhibition associated with the relative resistance of normal LTC-IC strongly supports the use of genistein for marrow purging.

受体和非受体蛋白质酪氨酸激酶（PTKs）在调控正常细胞和肿瘤细胞生长方面发挥关键作用。酪氨酸激酶抑制剂的可用性促使我们研究金雀异黄素的作用。 
作为天然的酪氨酸激酶抑制剂，我们研究它在体外金雀异黄素对多向造血祖细胞[CFU-Mix]，定向造血祖细胞[BFU- E]，粒-单系祖细胞[CFU-GM]，长期培养起始细胞（LTC-IC）和急性髓系白血病祖细胞（CFU-AML）的影响。 
递增剂量的金雀异黄素(1-100 微摩尔)连续暴露于正常骨髓细胞和血液单核非粘附细胞，血液CD34 + CD45RA-细胞和白血病胚细胞，导致对CFU-Mix, BFU-E, CFU-GM 和 CFU-AML剂量依赖性生长抑制作用，它具有显著的统计学意义（P<或= 0.05）。 
回归分析表明，金雀异黄素的浓度和生长抑制作用呈线性关系。和骨髓CFU-GM ID50(19 v 32微摩尔, P < or = 0.017)，未分离血细胞ID50 (19 v 44微摩尔, P < 或 = 0.028)和CD34+CD45RA-血细胞 ID50 (19 v 36, P < 或 = 0.04)相比，造成CFU-AML50％抑制(ID50)的金雀异黄素剂量明显降低。 
用金雀异黄素（200微摩尔）预处理白血病胚细胞1-2h后，发现CFU–AML比正常骨髓和血液的CFU–GM对金雀异黄素更敏感。预处理条件，以最大限度地抑制白血病和正常菌落生长，即骨髓（29 + / - 4％）和血液（40 + / - 3％）LTC-IC的百分比。 
总之，我们的数据表明： 
（1）金雀异黄素能有效抑制正常和白血病造血祖细胞的生长;
（2）生长抑制作用呈剂量和时间依赖性;
（3）白血病祖细胞比正常祖细胞对金雀异黄素的生长抑制更敏感;
（4）金雀异黄素对造血细胞施加直接毒性作用，同时保留相当比例的LTC-IC。有力的CFU - AML生长抑制与正常LTC-IC相关，这强烈支持金雀异黄素可用于净化骨髓。