Analysis of biologically active substances in volved in growth regulation of leukemia cells

我们评估了多种生物活性物质对白血病细胞生长调节的作用。我们发现具有费城染色体和11q23易位的白血病细胞的增殖受到粒细胞集落刺激因子（G-CSF）的刺激。此外，外源添加的抗G-CSF单克隆抗体部分抑制了它们的增殖，表明GCSF/G-CSF受体相互作用以自分泌机制参与了这些白血病细胞的生长调节。我们还发现，一种具有JAK-2活性的酪氨酸激酶特异性抑制剂（AG490）能够诱导诱导b前体白血病细胞，而不影响正常的造血干细胞，这表明使用这种药物可能有助于体外清除这些白血病细胞，用于自体干细胞移植。我们还发现，促红细胞生成素和瘦素对b前体白血病细胞的增殖具有中度刺激活性，而转化生长因子β具有明显的抑制活性。这些结果表明，这些生物活性物质与白血病细胞的命运密切相关，可能适用于白血病的治疗。

We evaluated effects of a variety of biologically active substances on growth regulation of leukemia cells. We found that proliferation of leukemic cells with Philadelphia chromosome and 11q23 translocation is stimulated by an addition of granulocyte colony-stimulating factor (G-CSF). Moreover, their proliferation was partially inhibited by exogenously added anti-G-CSF monoclonal antibody, suggesting that the GCSF/G-CSF receptor interaction is implicated in the growth regulation of these leukemia cells in a autocrine mechanism. We also showed that a specific inhibitor of tyrosine kinase having JAK-2 activity (AG490) was capable of inducing induction of B-precursor leukemia cells without effect on normal hematopoietic stem cells, suggesting that use of this drug might be useful for ex vivo purging of these leukemic cells for autologous stem cell transplantation. We also showed that erythropoietin and leptin have a moderate stimulatory activity on proliferation of B-precursor leukemia cells, whereas transforming growth factor β has a marked inhibitory activity. These results suggest that these biologically active substances are closely involved in determining destiny of leukemia cells and may be applicable for the treatment of leukemia.