Drach D, Estrov Z, Zhao S, Drach J, Cork A, Collins D, Kantarjian H, Andreeff M
Department of Hematology, University of Texas M. D. Anderson Cancer Center, Houston.
Leuk Lymphoma. 1994 Dec;16(1-2):79-88. doi: 10.3109/10428199409114143.
Cytokines are frequently used after chemotherapy of leukemias and solid tumors to augment recovery of normal hematopoiesis. While the regulation of normal and leukemic myelopoiesis is well investigated, little is known about effects of cytokines on growth and differentiation of lymphoblastic leukemia. In this study, we investigated the expression of receptors for G-CSF, GM-CSF, SCF, IL-3, and IL-7 on acute lymphoblastic leukemia (ALL) blasts and the effects of these growth factors (GF) on ALL blast colony formation. The binding of fluorescence-tagged cytokines to receptors on ALL blasts was studied by flow-cytometry in 27 cases of ALL (24 precursor B-ALL, 3 T-ALL). Receptor-binding for myeloid-associated GF was observed in the majority of precursor B-ALL (G-CSF = 100%, GM-CSF = 65%, IL-3 = 83%, SCF = 74%), but not in T-ALL. Binding of labelled IL-7 was detected in both precursor B- (92%) and T-ALL (100%). The presence of receptors for SCF in ALL was confirmed by polymerase chain reaction for c-kit mRNA in 19/21 cases tested. Expression of receptors for G-CSF, GM-CSF, IL-3, and SCF was not associated with expression of myeloid antigens, or with specific cytogenetic abnormalities. The effects of these GF on clonogenic cells were tested in the ALL blast colony assay and varied between samples, but all cytokines were able to increase clonogenic growth. The GM-CSF/IL-3 fusion molecule PIXY-321 was most effective in promoting colony growth. In some cases inhibition of colony formation was found. We conclude that ALL blast cells have receptors not only for IL-7, but also for G-CSF, GM-CSF, SCF, and IL-3. ALL precursors can respond to these GF with changes in their clonogenic growth indicating the presence of functional receptors. Results may have implications for therapeutic approaches combining cytokines and chemotherapy.
细胞因子常用于白血病和实体瘤化疗后，以促进正常造血功能的恢复。虽然对正常和白血病髓系造血的调控已有充分研究，但关于细胞因子对淋巴细胞白血病生长和分化的影响却知之甚少。在本研究中，我们调查了急性淋巴细胞白血病（ALL）原始细胞上G-CSF、GM-CSF、SCF、IL-3和IL-7受体的表达，以及这些生长因子（GF）对ALL原始细胞集落形成的影响。通过流式细胞术研究了27例ALL（24例前体B-ALL，3例T-ALL）中荧光标记细胞因子与ALL原始细胞上受体的结合情况。在大多数前体B-ALL中观察到与髓系相关GF的受体结合（G-CSF = 100%，GM-CSF = 65%，IL-3 = 83%，SCF = 74%），但在T-ALL中未观察到。在标记的IL-7与前体B-ALL（92%）和T-ALL（100%）中均检测到结合。通过对19/21例检测样本进行c-kit mRNA的聚合酶链反应，证实了ALL中SCF受体的存在。G-CSF、GM-CSF、IL-3和SCF受体的表达与髓系抗原的表达或特定细胞遗传学异常无关。在ALL原始细胞集落试验中测试了这些GF对克隆形成细胞的影响，不同样本之间存在差异，但所有细胞因子都能够增加克隆形成生长。GM-CSF/IL-3融合分子PIXY-321在促进集落生长方面最有效。在某些情况下发现了集落形成的抑制。我们得出结论，ALL原始细胞不仅有IL-7受体，还有G-CSF、GM-CSF、SCF和IL-3受体。ALL前体可以对这些GF作出反应，其克隆形成生长发生变化，表明存在功能性受体。这些结果可能对细胞因子与化疗联合的治疗方法具有启示意义。
