Human Gene Set: PARK_TRETINOIN_RESPONSE_AND_RARA_PLZF_FUSION


Standard name PARK_TRETINOIN_RESPONSE_AND_RARA_PLZF_FUSION
Systematic name M11798
Brief description Genes up-regulated by tretinoin (ATRA) [PubChem=444795] in U937 cells (acute promyelocytic leukemia, APL) made resistant to the drug by expression of the PLZF-RARA fusion [GeneID=7704] [GeneID=5914].
Full description or abstract Acute promyelocytic leukemia (APL) is associated with chromosomal translocations involving retinoic acid receptor alpha (RAR alpha) and its fusion partners including promyelocytic leukemia (PML) and promyelocytic leukemia zinc finger (PLZF). Using oligonucleotide arrays, we examined changes in global gene expression mediated by the ectopic expression of either PML/RAR alpha (retinoid-sensitive) or PLZF/RAR alpha (retinoid-resistant) in U937 cells. Of more than 5000 genes analyzed, 16 genes were commonly up-regulated, and 57 genes were down-regulated by both fusion proteins suggesting their role in the APL phenotype. In our APL model, for example, TNFAIP2, TNFR2, ELF4, RAR gamma, and HoxA1 were down-regulated by both fusion proteins in the absence of retinoic acid (RA). RA strongly up-regulated these genes in PML/RAR alpha, but not in PLZF/RAR alpha expressing U937 cells. Expression studies in NB4, retinoid-resistant NB4-R2, normal human CD34+ cells, and APL patient samples strongly suggest their role in the regulation of granulocytic differentiation. Furthermore, combined treatment with tumor necrosis factor alpha (TNF alpha) and RA synergistically enhanced granulocytic differentiation in NB4 cells but not in NB4-R2 cells. Our data indicate that APL pathogenesis and retinoid-induced granulocytic differentiation of APL cells involve genes in the cell death pathway, and that cooperation between the RA and TNFalpha signaling pathways exists. Targeting both the retinoid-dependent differentiation and the cell death pathways may improve leukemic therapy, especially in retinoid-resistant acute myeloid leukemia.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12893766   Authors: Park DJ,Vuong PT,de Vos S,Douer D,Koeffler HP
Exact source Table 2: U937B412 (PLZF/RARalpha)
Related gene sets (show 4 additional gene sets from the source publication)

(show 13 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform or
identifier namespace		 AFFY_HuGene
Dataset references  
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 ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 23 genes
Gene families ? Categorize these 23 genes by gene family
Show members (show 26 source identifiers mapped to 23 genes)
Version history  

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