Santoli D, Yang Y C, Clark S C, Kreider B L, Caracciolo D, Rovera G
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
J Immunol. 1987 Nov 15;139(10):3348-54.
Three human leukemia cell lines (TALL-101, AML-193, and MV4-11) that require granulocyte/macrophage-colony stimulating factor (GM-CSF) for growth in a chemically defined medium were examined for their response to recombinant human (rh) cytokines. Either rh interleukin (IL)-3 or rhGM-CSF alone supported the long term growth of all three cell lines, and the two growth factors acted synergistically to stimulate the proliferation of the early T lymphoblastic leukemia (TALL-101) and of the monocytic leukemia (AML-193) cells. However, IL-3 antagonized the proliferation of the biphenotypic B-myelomonocytic leukemia (MV4-11) cells in the presence of GM-CSF when both factors were used at very low concentrations. The rh granulocyte (G)-CSF independently supported the long and short term growth of AML-193 and MV4-11, respectively, and synergized with GM-CSF in inducing proliferation of these cells. By contrast, G-CSF did not stimulate TALL-101 cell growth and antagonized the effect of GM-CSF such that proliferation was arrested. Although neither rh macrophage (M)-CSF nor rhIL-1 alpha independently promoted proliferation of the three leukemia cell lines, these cytokines were able to either up- or down-regulate the GM-CSF-dependent growth of these cells. Taken together, these data demonstrate that leukemic cells often require the synergistic action of several cytokines for optimal growth, whereas other combinations of factors may be growth-inhibitory. This raises the possibility that multiple hemopoietic growth factors sustain or control leukemic cell proliferation also in vivo. In addition, the observation the G-CSF, M-CSF, and IL-1 alpha can, in some cases, arrest cell proliferation without inducing differentiation suggests that the programs of proliferative arrest and differentiation in leukemic cells can be dissociated.
三种在化学成分明确的培养基中生长需要粒细胞/巨噬细胞集落刺激因子（GM-CSF）的人白血病细胞系（TALL-101、AML-193和MV4-11）被检测对重组人（rh）细胞因子的反应。单独的rh白细胞介素（IL）-3或rhGM-CSF均可支持所有三种细胞系的长期生长，并且这两种生长因子协同作用以刺激早期T淋巴细胞白血病（TALL-101）和单核细胞白血病（AML-193）细胞的增殖。然而，当两种因子都以非常低的浓度使用时，在GM-CSF存在的情况下，IL-3会拮抗双表型B-髓单核细胞白血病（MV4-11）细胞的增殖。rh粒细胞（G）-CSF分别独立支持AML-193和MV4-11的长期和短期生长，并与GM-CSF协同诱导这些细胞的增殖。相比之下，G-CSF不刺激TALL-101细胞生长，并拮抗GM-CSF的作用，从而使增殖停止。虽然rh巨噬细胞（M）-CSF和rhIL-1α单独均不促进这三种白血病细胞系的增殖，但这些细胞因子能够上调或下调这些细胞依赖GM-CSF的生长。综上所述，这些数据表明白血病细胞通常需要几种细胞因子的协同作用才能实现最佳生长，而其他因子组合可能具有生长抑制作用。这增加了多种造血生长因子在体内也维持或控制白血病细胞增殖的可能性。此外，观察到G-CSF、M-CSF和IL-1α在某些情况下可在不诱导分化的情况下阻止细胞增殖，这表明白血病细胞中增殖停滞和分化的程序可以分离。
