Gene Set: HESS_TARGETS_OF_HOXA9_AND_MEIS1_UP

Standard name HESS_TARGETS_OF_HOXA9_AND_MEIS1_UP
Systematic name M1319
Brief description Genes up-regulated in hematopoietic precursor cells conditionally expressing HOXA9 and MEIS1 [GeneID=3205;4211].
Full description or abstract Abdominal-type HoxA genes in combination with Meis1 are well-documented on-cogenes in various leukemias but it is unclear how they exert their transforming function. Here we used a system of conditional transformation by an inducible mixed lineage leukemia-eleven-nineteen leukemia (MLL-ENL) oncoprotein to overexpress Hoxa9 and Meis1 in primary hematopoietic cells. Arrays identified c-Myb and a c-Myb target (Gstm1) among the genes with the strongest response to Hoxa9/Meis1. c-Myb overexpression was verified by Northern blot and quantitative reverse transcription-polymerase chain reaction (RT-PCR). Also MLL-ENL activated c-Myb through up-regulation of Hoxa9 and Meis1. Consequently, short-term suppression of c-Myb by small inhibitory RNA (siRNA) efficiently inhibited transformation by MLL-ENL but did not impair transformation by transcription factor E2A-hepatic leukemia factor (E2A-HLF). The anti c-Myb siRNA effect was abrogated by coexpression of a c-Myb derivative with a mutated siRNA target site. The introduction of a dominant-negative c-Myb mutant had a similar but weaker effect on MLL-ENL-mediated transformation. Hematopoietic precursors from mice homozygous for a hypo-morphic c-Myb allele were more severely affected and could be transformed neither by MLL-ENL nor by E2A-HLF. Ectopic expression of c-Myb induced a differentiation block but c-Myb alone was not transforming in a replating assay similar to Hoxa9/Meis1. These results suggest that c-Myb is essential but not sufficient for Hoxa9/Meis1 mediated transformation.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16507773   Authors: Hess JL,Bittner CB,Zeisig DT,Bach C,Fuchs U,Borkhardt A,Frampton J,Slany RK
Exact source Table 1S
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Organism Mus musculus
Contributed by Kevin Vogelsang (MSigDB Team)
Source platform AFFY_Mouse430
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Version history 3.0: Renamed from HESS_HOXAANMEIS1_UP

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