Human Gene Set: WANG_TARGETS_OF_MLL_CBP_FUSION_DN

For the Mouse gene set with the same name, see WANG_TARGETS_OF_MLL_CBP_FUSION_DN

Standard name WANG_TARGETS_OF_MLL_CBP_FUSION_DN
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
      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 297 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Mus musculus
Contributed by Kevin Vogelsang (MSigDB Team)
Source platform or
identifier namespace
MOUSE_SEQ_ACCESSION
Dataset references (show 1 datasets)
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 46 genes
Gene families ? Categorize these 46 genes by gene family
Show members (show 47 source identifiers mapped to 46 genes)
Version history 3.1: First introduced

We need your help: Update on GSEA/MSigDB funding support

Last November we submitted a proposal to NCI's Information Technology for Cancer Research (ITCR) program for the continued funding of GSEA and MSigDB. Unfortunately, our proposal was not funded in this round, but we were encouraged to resubmit for the next one. This funding is critical for our continuing support and enhancement of the GSEA-MSigDB resource.

For our original submission many of you sent us emails of support, an important requirement for these grants. We now ask for your help again. We would greatly appreciate a short email message from you describing how the resource has been of value to your work and any concerns you may have about its continued availability.

Please send us your message of support to gsea-los@broadinstitute.org on or before Monday June 5, 2023.

Thanks in advance for your help and support.
The GSEA/MSigDB Team.


See MSigDB license terms here. Please note that certain gene sets have special access terms.