Systematic name M1455
Brief description Top 50 genes down-regulated in granulocyte/macrophage progenitors (GMP) upon expression of MLL-CBP fusion [GeneID=4297;1387].
Full description or abstract Chromosomal translocations that fuse the mixed lineage leukemia (MLL) gene with multiple partners typify acute leukemias of infancy as well as therapy-related leukemias. We utilized a conditional knockin strategy to bypass the embryonic lethality caused by MLL-CBP expression and to assess the immediate effects of induced MLL-CBP expression on hematopoiesis. Within days of activating MLL-CBP, the fusion protein selectively expanded granulocyte/macrophage progenitors (GMP) and enhanced their self-renewal/proliferation. MLL-CBP altered the gene expression program of GMP, upregulating a subset of genes including Hox a9. Inhibition of Hox a9 expression by RNA interference demonstrated that MLL-CBP required Hox a9 for its enhanced cell expansion. Following exposure to sublethal gamma-irradiation or N-ethyl-N-nitrosourea (ENU), MLL-CBP mice developed myelomonocytic hyperplasia and progressed to fatal myeloproliferative disorders. These represented the spectrum of therapy-induced acute myelomonocytic leukemia/chronic myelomonocytic leukemia/myelodysplastic/myeloproliferative disorder similar to that seen in humans possessing the t(11;16). This model of MLL-CBP therapy-related myeloproliferative disease demonstrates the selectivity of this MLL fusion for GMP cells and its ability to initiate leukemogenesis in conjunction with cooperating mutations.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 15635450   Authors: Wang J,Iwasaki H,Krivtsov A,Febbo PG,Thorner AR,Ernst P,Anastasiadou E,Kutok JL,Kogan SC,Zinkel SS,Fisher JK,Hess JL,Golub TR,Armstrong SA,Akashi K,Korsmeyer SJ
Exact source Fig 5: Downregulated
Related gene sets (show 1 additional gene sets from the source publication)

(show 295 gene sets from the same authors)
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Organism Mus musculus
Contributed by Kevin Vogelsang (MSigDB Team)
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Human tissue compendium (Novartis)
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NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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