Gene Set: KAMIKUBO_MYELOID_MN1_NETWORK

Standard name KAMIKUBO_MYELOID_MN1_NETWORK
Systematic name M2093
Brief description Network of differentially expressed myeloid genes centered around MN1 [GeneID=4330].
Full description or abstract Dominant RUNX1 inhibition has been proposed as a common pathway for CBF leukemia. CBF beta-SMMHC, a fusion protein in human acute myeloid leukemia (AML), dominantly inhibits RUNX1 largely through its RUNX1 high-affinity binding domain (HABD). However, the type I CBF beta-SMMHC fusion in AML patients lacks HABD. Here, we report that the type I CBF beta-SMMHC protein binds RUNX1 inefficiently. Knockin mice expressing CBF beta-SMMHC with a HABD deletion developed leukemia quickly, even though hematopoietic defects associated with Runx1-inhibition were partially rescued. A larger pool of leukemia-initiating cells, increased MN1 expression, and retention of RUNX1 phosphorylation are potential mechanisms for accelerated leukemia development in these mice. Our data suggest that RUNX1 dominant inhibition may not be a critical step for leukemogenesis by CBF beta-SMMHC.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 20478528   Authors: Kamikubo Y,Zhao L,Wunderlich M,Corpora T,Hyde RK,Paul TA,Kundu M,Garrett L,Compton S,Huang G,Wolff L,Ito Y,Bushweller J,Mulloy JC,Liu PP
Exact source Table 2S
Related gene sets (show 1 additional gene sets from the source publication)

(show 11 gene sets from the same authors)
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Organism Mus musculus
Contributed by Arthur Liberzon (Broad Institute)
Source platform Mouse430_2
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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