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

Abstract

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.

DOI: 10.1016/j.leukres.2010.08.011

Cite this paper

@article{Kumar2011t411LD, title={t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL.}, author={Amit Kumar and Qing Yao and Quanzhi Li and Thien A Sam and John H. Kersey}, journal={Leukemia research}, year={2011}, volume={35 3}, pages={305-9} }