Genes regulated by Meis1 in murine Mll-AF9 leukemia cells

Leukemias with MLL-rearrangements are characterized by high expression of the homeo box gene MEIS1. In these studies, we knocked down Meis1 expression by shRNA lentivirus transduction in murine Mll-AF9 leukemia cells. Meis1 knockdown resulted in decreased proliferation and survival of murine Mll-AF9 leukemia cells. We also observed reduced clonogenic capacity and increased monocytic differentiation. The establishment of leukemia in transplant recipients was significantly delayed by Meis1 knockdown. Gene expression profiling of cells transduced with Meis1 shRNA showed reduced expression of genes associated with cell cycle entry and progression. shRNA mediated knockdown of MEIS1 in human MLL-fusion gene leukemia cell lines resulted in reduced cell growth. These results show that MEIS1 expression is important for MLL-rearranged leukemias and suggest that MEIS1 promotes cell cycle entry. Targeting MEIS1 may have therapeutic potential for treating leukemias expressing this transcription factor. Keywords: Gene expression Murine Mll-AF9 leukemia (4166) cells were transduced with lentivirus expressing shRNA against Meis1 or control lentivirus (empty vector). Gene expression profiles were compared at 48 hours post transduction, using Puromycin as selection agent for transduced cells.