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<MSIGDB BUILD_DATE="Jan 29, 2026" VERSION="2026.1.Hs" NAME="export">
    <GENESET STANDARD_NAME="BRACHAT_RESPONSE_TO_METHOTREXATE_DN" SYSTEMATIC_NAME="M1498" HISTORICAL_NAMES="" PMID="12447701" AUTHORS="Brachat A,Pierrat B,Xynos A,Brecht K,Simonen M,Brüngger A,Heim J" GEOID="" EXACT_SOURCE="Table 1 &amp; 2: Methotrexate" GENESET_LISTING_URL="" EXTERNAL_DETAILS_URL="" CHIP="MOUSE_SEQ_ACCESSION" CONTRIBUTOR="John Newman" CONTRIBUTOR_ORG="University of Washington" DESCRIPTION_BRIEF="Genes down-regulated in  FL5.12 cells (pro-B lymphocyte) in response to methotrexate [PubChem=4112]." DESCRIPTION_FULL="DNA microarrays are powerful tools for the analysis of gene expression on a genomic scale. The importance of individual regulatory events for the process under study can however not be deduced unequivocally without additional experiments. We devised a strategy to identify central regulators of cancer drug responses by combining the results of microarray experiments with efficient methods for phenotypic testing of candidate genes. We exposed murine FL5.12 pro-B cells to cisplatin, camptothecin, methotrexate or paclitaxel, respectively and analysed the patterns of gene expression with cDNA microarrays. Drug-specific regulatory events as well as intersections between different apoptotic pathways, including previously studied responses to staurosporine and interleukin-3 (IL-3) deprivation, were identified. Genes shared by at least three pathways were chosen for further analysis. Ectopic expression of three such genes, TEAP, GP49B, and Lipin1 was found to have an anti-proliferative effect on pro-B cells. Interestingly, we identified hemoglobin alpha as a strong pro-apoptotic regulator. While hemoglobin-expressing cells were growing normally in the presence of IL-3, they displayed accelerated apoptosis with similar kinetics as Bax overexpressing cells upon IL-3 removal. The pro-apoptotic effect of hemoglobin was suppressed by Bcl-2 and was characterized by enhanced stimulation of caspase activity." TAGS="" MEMBERS="AA024085,AA024088,AA028342,AA048837,AA051654,AA060500,AA108822,AA122891,AA182992,AA185446,AA197519,AA204262,AA212445,AA217366,AA265396,AA276216,AA289992,AA397114,AA414831,AA434709,AA499926,AA518639,AA521758,AI595466,AI892192,W11965,W82313" MEMBERS_SYMBOLIZED="AK4,ALDOA,ANXA4,BCL2,BNIP3L,CORO7,EMILIN2,ENO1,ENO3,FKBP3,GAPDH,GPI,HIGD1A,HIKESHI,HMGCS1,IFITM2,IFITM3,MIA2,MT1F,NDUFV3,OSTF1,PDK3,PPIA,SASH3,SLC25A1,STAT5A" MEMBERS_EZID="10410,10581,2023,2027,205,226,2287,2597,25994,26578,2821,307,3157,4253,4494,4731,51501,5165,54440,5478,596,6576,665,6776,79585,84034" MEMBERS_MAPPING="AA024085,EMILIN2,84034|AA024088,OSTF1,26578|AA028342,BNIP3L,665|AA048837,IFITM3,10410|AA051654,MT1F,4494|AA060500,MIA2,4253|AA108822,SLC25A1,6576|AA122891,GAPDH,2597|AA182992,FKBP3,2287|AA185446,SASH3,54440|AA197519,BCL2,596|AA204262,ENO1,2023|AA212445,STAT5A,6776|AA217366,PDK3,5165|AA265396,null,null|AA276216,GPI,2821|AA289992,IFITM2,10581|AA397114,ANXA4,307|AA414831,HIGD1A,25994|AA434709,HIKESHI,51501|AA499926,PPIA,5478|AA518639,ALDOA,226|AA521758,NDUFV3,4731|AI595466,CORO7,79585|AI892192,HMGCS1,3157|W11965,ENO3,2027|W82313,AK4,205" FILTERED_BY_SIMILARITY="" FOUNDER_NAMES="" REFINEMENT_DATASETS="" VALIDATION_DATASETS="" CATEGORY_CODE="C2" ORGANISM="Mus musculus" SUB_CATEGORY_CODE="CGP"/>
</MSIGDB>
