串联重复的Flt3组成性激活STAT5和丝裂原活化蛋白激酶，并在白细胞介素-3依赖的细胞系中引发自主细胞生长。
Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines.
作者信息
Hayakawa F, Towatari M, Kiyoi H, Tanimoto M, Kitamura T, Saito H, Naoe T
机构信息
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
出版信息
Oncogene. 2000 Feb 3;19(5):624-31. doi: 10.1038/sj.onc.1203354.
We have recently identified an internal tandem duplication of the human Flt3 gene in approximately 20% of acute myeloid leukemia (AML) cases. In the present study, the wild-type and the mutant Flt3 genes were transfected into two IL-3-dependent cell lines, 32D and BA/F3 cells. Mutant Flt3-transfected cells exhibited autonomous growth while wild-type Flt3-transfected cells with the continuous stimulation of Flt3 ligand exhibited a minimal proliferation. Cells expressing mutant Flt3 showed constitutive activation of STAT5 and MAP kinase. In contrast, Flt3 ligand stimulation caused rapid activation of MAP kinase but not STAT5 in cells expressing wild-type Flt3. Finally, we found constitutive activation of MAP kinase and STAT5 in all clinical samples of AML patients with mutant Flt3. Our study shows the significance of internal tandem duplication of Flt3 receptors for leukemia cell expansion.
我们最近在大约20%的急性髓系白血病（AML）病例中发现了人类Flt3基因的内部串联重复。在本研究中，野生型和突变型Flt3基因被转染到两种依赖白细胞介素-3的细胞系，即32D细胞和BA/F3细胞中。转染了突变型Flt3的细胞表现出自主生长，而在持续受到Flt3配体刺激的情况下，转染了野生型Flt3的细胞增殖极少。表达突变型Flt3的细胞显示出STAT5和丝裂原活化蛋白激酶（MAP激酶）的组成性激活。相比之下，Flt3配体刺激在表达野生型Flt3的细胞中导致MAP激酶迅速激活，但不会导致STAT5激活。最后，我们在所有携带突变型Flt3的AML患者临床样本中发现了MAP激酶和STAT5的组成性激活。我们的研究表明Flt3受体内部串联重复对白血病细胞扩增具有重要意义。
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