Gene Set: KUMAR_TARGETS_OF_MLL_AF9_FUSION

Standard name KUMAR_TARGETS_OF_MLL_AF9_FUSION
Systematic name M3284
Brief description Myeloid leukemia model in mice with germ-line MLL-AF9 fusion knock-in [GeneID=4297;4300]: genes changed in comparison among the leukemic, preleukemic and wild-type animals.
Full description or abstract Identification of the targets of mixed lineage leukemia (MLL) fusion genes will assist in understanding the biology of MLL fusion gene leukemias and in development of better therapies. Numerous studies have implicated HOXA9 as one of the possible targets of MLL fusion proteins. To determine if HOXA9 was required for leukemia development by MLL fusion genes, we compared the effects of the Mll-AF9 knock-in mutation in mice in the presence or absence of Hoxa9. Both groups of mice showed myeloid expansion at 8 weeks and then developed myeloid leukemia with a similar incidence and time course. The leukemia in the mice lacking Hoxa9 generally displayed a more immature myeloid phenotype than that in the mice that were wild-type for Hoxa9. Gene expression profiling revealed that expression of Mll-AF9 led to overexpression of Hoxa5, Hoxa6, Hoxa7, Hoxa9, and Hoxa10. Thus, genes of the Hox-a cluster are important in defining the phenotype but not the incidence of Mll-AF9 leukemia. These results demonstrate that the Mll-AF9 fusion gene disrupts the expression of several Hox genes, none of which as a single gene is likely to be necessary for development of leukemia. Instead, we propose that the Hox code minimally defined by the Hoxa5-a9 cluster is central to MLL leukemogenesis.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 14615372   Authors: Kumar AR,Hudson WA,Chen W,Nishiuchi R,Yao Q,Kersey JH
Exact source Table 1S
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Organism Mus musculus
Contributed by Kevin Vogelsang (MSigDB Team)
Source platform AFFY_MG_U74
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Version history 3.0: Renamed from KUMAR_HOXA_DIFF

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