Genetic complementation of cytokine signaling identifies central role of kinases in hematopoietic cell proliferation
Genetic complementation of cytokine signaling identifies central role of kinases in hematopoietic cell proliferation
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DOI：
10.1038/sj.onc.1207209
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发表时间：
2004-02-12
期刊：
影响因子：
8
通讯作者：
Daley, GQ
中科院分区：
文献类型：
--
作者：
Koh, EY;Chen, T;Daley, GQ
分子证据表明急性白血病的发生有一个多步骤的过程。由于细胞因子信号级联的不适当激活是人类白血病中反复出现的主题，因此我们进行了表达筛选以鉴定转化细胞因子依赖性细胞的基因。利用来自骨髓增殖性疾病患者外周血单个核细胞的逆转录病毒cDNA文库，我们分离了许多基因，这些基因在遗传上补充了BaF/3和TF-1细胞增殖所需的细胞因子。大多数恢复的基因代表了激酶家族的成员，包括几个先前与白血病发生有关的基因。我们的无偏见筛选突出了激酶激活在造血细胞增殖中的核心作用，并确定了许多潜在的白血病癌蛋白。
Molecular evidence suggests a multistep process in the development of acute leukemia. Since inappropriate activation of cytokine signaling cascades is a recurring theme in human leukemia, we performed expression screens to identify genes that transform cytokine-dependent cells. Using retroviral cDNA libraries derived from peripheral blood mononuclear cells of patients with myeloproliferative disorders, we isolated numerous genes that genetically complement cytokine requirements for proliferation of BaF/3 and TF-1 cells. The majority of recovered genes represent members of the kinase family, including several previously linked to leukemogenesis. Our unbiased screen highlights the central role of kinase activation in hematopoietic cell proliferation and identifies a number of potential leukemic oncoproteins.