Ikeda H, Kanakura Y, Furitsu T, Kitayama H, Sugahara H, Nishiura T, Karasuno T, Tomiyama Y, Yamatodani A, Kanayama Y
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Exp Hematol. 1993 Dec;21(13):1686-94.
The interaction of the proto-oncogene c-kit product with its ligand (stem cell factor or SCF) is considered to play crucial roles in hematopoiesis. In a series of human acute myeloblastic leukemia (AML) cells, the effects of recombinant human (rh) SCF on AML cells were examined in short-term and long-term cultures. c-kit expression was detected in 26 of 31 AML cases, and short-term treatment of AML cells with rhSCF led to proliferation in 13 of 18 AML cases that expressed the c-kit product. In seven of the 13 cases showing proliferative response to rhSCF, AML cells were exclusively composed of immature blast cells. We therefore used the seven AML cases for examining the effect of rhSCF on the differentiation and proliferation of AML cells in a long-term culture. Proliferation of AML cells was found to be maintained with rhSCF more than 2 weeks in five of seven cases and 4 weeks in two cases, whereas most of the AML cells died before 2 weeks in the absence of rhSCF. Further, in four of five AML cases, all of which expressed the CD34 antigen and showed a proliferative response to rhSCF in a long-term culture, rhSCF appeared to promote differentiation of blast cells toward lineages of various cell types, such as granulocytic and/or monocytic and mast-cell lineages. These results suggest that, at least in a fraction of AML cases, rhSCF can induce not only proliferation but also differentiation of AML cells, and also that phenotypic manifestation of AML cells may not mean definite cell commitment but can be changed by stimulation with rhSCF.
原癌基因c-kit产物与其配体（干细胞因子或SCF）的相互作用被认为在造血过程中起关键作用。在一系列人类急性髓性白血病（AML）细胞中，研究了重组人（rh）SCF在短期和长期培养中对AML细胞的影响。在31例AML病例中的26例检测到c-kit表达，用rhSCF对AML细胞进行短期处理后，在18例表达c-kit产物的AML病例中有13例出现增殖。在对rhSCF有增殖反应的13例病例中的7例中，AML细胞仅由未成熟的母细胞组成。因此，我们使用这7例AML病例来研究rhSCF在长期培养中对AML细胞分化和增殖的影响。发现7例病例中有5例的AML细胞在rhSCF作用下增殖维持超过2周，2例维持4周，而在没有rhSCF的情况下，大多数AML细胞在2周前死亡。此外，在长期培养中对rhSCF有增殖反应且均表达CD34抗原的5例AML病例中的4例中，rhSCF似乎促进母细胞向各种细胞类型的谱系分化，如粒细胞和/或单核细胞谱系以及肥大细胞谱系。这些结果表明，至少在一部分AML病例中，rhSCF不仅可以诱导AML细胞增殖，还可以诱导其分化，而且AML细胞的表型表现可能并不意味着确定的细胞定向，但可以通过rhSCF刺激而改变。
