t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL

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• 作者：Ashish R. Kumar^a ; ^b ; ^{ashish.kumar@cchmc.org} ; Qing Yao^a ; Quanzhi Li^a ; Thien A. Sam^a ; John H. Kersey^a ; ^b ; ^c
• 关键词：MLL ; AF4 ; t(4 ; 11) ; Leukemia ; 11q23
• 刊名：Leukemia Research
• 出版年：2011
• 出版时间：March 2011
• 年：2011
• 卷：35
• 期：3
• 页码：305-309
• 全文大小：635 K

文摘

The most frequent MLL-gene rearrangement found in leukemia is a reciprocal translocation with AF4 on chromosome 4 resulting in the formation of the MLL-AF4 and the AF4-MLL fusion genes. The oncogenic role of MLL-AF4 is documented but the significance of the reciprocal product – AF4-MLL in leukemia is less clear. In the human leukemia cell lines – RS4;11 and SEMK2-M1, both of which express MLL-AF4 and AF4-MLL, we knocked down the expression of AF4-MLL using siRNA. Loss of AF4-MLL had no effect on the growth of either RS4;11 or SEMK2-M1 cells. Furthermore, in SEMK2-M1 cells there were no changes in cell cycle or apoptosis with loss of AF4-MLL. In contrast, knockdown of MLL-AF4 significantly inhibited growth of both RS4;11 and SEMK2-M1. Additionally, in SEMK2-M1 cells, loss of MLL-AF4 led to G2/M cell cycle arrest and increased apoptosis. Overall, these results demonstrate that in t(4;11) leukemia, the MLL-AF4 fusion protein is critical for leukemia cell proliferation and survival while the AF4-MLL fusion product is dispensable.