The p21Waf1 pathway is involved in blocking leukemogenesis by the t(8;21) fusion protein AML1-ETO.
The p21Waf1 pathway is involved in blocking leukemogenesis by the t(8;21) fusion protein AML1-ETO.
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DOI：
10.1182/blood-2006-03-012575
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发表时间：
2007-05
期刊：
影响因子：
20.3
通讯作者：
L. Peterson;Ming Yan;Dong-er Zhang
中科院分区：
文献类型：
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作者：
L. Peterson;Ming Yan;Dong-er Zhang
8;21易位是M2分类的急性髓性白血病（AML）的主要促成因素，发生在这些病例的约40%中。使用该融合蛋白的多个小鼠模型证明，AML 1-ETO需要二次致突变事件来促进白血病发生。在这里，我们表明，负细胞周期调节因子p21（WAF 1）基因的上调AML 1-ETO在蛋白质，RNA和启动子水平。逆转录病毒转导和p21（WAF 1）缺陷细胞的造血细胞移植实验表明，AML 1-ETO能够在p21（WAF 1）缺失的情况下促进白血病发生。因此，p21（WAF 1）的缺失促进了AML 1-ETO诱导的白血病发生，表明p21（WAF 1）途径中的突变事件绕过了AML 1-ETO诱导的p21（WAF 1）表达的生长抑制作用，可能是AML 1-ETO相关急性髓性白血病的重要因素。
The 8;21 translocation is a major contributor to acute myeloid leukemia (AML) of the M2 classification occurring in approximately 40% of these cases. Multiple mouse models using this fusion protein demonstrate that AML1-ETO requires secondary mutagenic events to promote leukemogenesis. Here, we show that the negative cell cycle regulator p21(WAF1) gene is up-regulated by AML1-ETO at the protein, RNA, and promoter levels. Retroviral transduction and hematopoietic cell transplantation experiments with p21(WAF1)-deficient cells show that AML1-ETO is able to promote leukemogenesis in the absence of p21(WAF1). Thus, loss of p21(WAF1) facilitates AML1-ETO-induced leukemogenesis, suggesting that mutagenic events in the p21(WAF1) pathway to bypass the growth inhibitory effect from AML1-ETO-induced p21(WAF1) expression can be a significant factor in AML1-ETO-associated acute myeloid leukemia.