Systematic name M4385
Brief description Genes up-regulated in NB4 cells (acute promyelocytic leukemia, APL) by tretinoin [PubChem=444795] alone.
Full description or abstract Differentiation induction is an effective therapy for acute promyelocytic leukemia (APL), which dramatically responds to all-trans-retinoic acid (ATRA). Recent studies have indicated that combinatorial use of retinoid and nonretinoid compounds, such as histone deacetylase inhibitors, arsenics, and PKA agonists, has higher therapeutic value in this disease and potentially in other malignancies. In a screen of 370 compounds, we identified benzodithiophene analogues as potent enhancers of ATRA-induced APL cell differentiation. These effects were not associated with changes in global histone acetylation and, for the most potent compounds, were exerted at very low nanomolar concentrations, and were paralleled by enhancement of some, but not all, ATRA-modulated gene expressions. Investigating the mechanism underlying the effects of these drugs on ATRA-induced APL cell differentiation, we have shown that benzodithiophenes enhance ATRA-mediated dissociation and association of corepressor N-CoR and coactivator p300 acetyltransferase, respectively, with retinoic acid receptor (RAR) alpha proteins. These data suggest that benzodithiophenes act at the level of receptor activation, possibly by affecting posttranslational modification of the receptor (and/or coregulators), thus leading to an enhancement in ATRA-mediated effects on gene expression and APL cell differentiation. Given the specificities of these low benzodithiophene concentrations for PML-RARalpha and RARalpha, these drugs may be useful for combinatorial differentiation therapy of APL and possibly other acute myelogenous leukemia subtypes in which the overall ATRA signaling is suppressed.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16140955   Authors: Xu K,Guidez F,Glasow A,Chung D,Petrie K,Stegmaier K,Wang KK,Zhang J,Jing Y,Zelent A,Waxman S
Exact source Table 2A
Related gene sets (show 3 additional gene sets from the source publication)

(show 104 gene sets from the same authors)
External links  
Filtered by similarity
Organism Homo sapiens
Contributed by Kevin Vogelsang (MSigDB Team)
Dataset references  
Download gene set format: grp | text | gmt | gmx | xml
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 16 genes
Gene families Categorize these 16 genes by gene family
Show members (show 16 members mapped to 16 genes)
Version history 3.0: Renamed from XU_ATRA_UP

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