{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE253nnn/GSE253138/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":[" Mus musculus","Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE253138"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A dual role for PSIP1/LEDGF in T-cell acute lymphoblastic leukemia [RNA-seq]","description":"T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Although intensified therapeutic protocols have improved the outcome of T-ALL patients, they coincide with severe short- and long-term side effects. In addition, no salvage therapeutic strategies are available for primary therapy-resistant or relapsed T-ALL, resulting in a dismal outcome for these patients. It highlights the need to identify new targets in T-ALL biology that allow the development of less toxic targeted therapies. PSIP1, a histone mark reader, is a dependency factor in KMT2A-rearranged myeloid leukemia, but is dispensable for normal hematopoiesis, making it an attractive therapeutic target. Nonetheless, rare recurrent inactivating mutations and deletions of PSIP1, suggest that PSIP1 could act as a tumor suppressor in T-ALL. Here, we demonstrate that the loss of Psip1 accelerates T-ALL initiation in mice and we identified a correlation with reduced H3K27me3 binding. Contrastingly, loss of PSIP1 impaired cell proliferation in several human and murine T-ALL cell lines. In these cell lines, PSIP1 loss leads to a significant downregulation of COX20, an assembly factor of the cytochrome c oxidase in the mitochondria, and is associated with a reduction in mitochondrial respiration. Similarly to what was observed for PSIP1, loss of COX20 expression also leads to an impairment of proliferation in these T-ALL cell lines. These data corroborate that PSIP1 can exert a dual role in the context of T-ALL, either as a tumor suppressor gene during tumor initiation or as a dependency factor in tumor maintenance.","dates":{"publication":"2024/10/20"},"accession":"GSE253138","cross_references":{"GSM":["GSM8014797","GSM8014830","GSM8014796","GSM8014799","GSM8014810","GSM8014832","GSM8014831","GSM8014798","GSM8014834","GSM8014812","GSM8014833","GSM8014811","GSM8014814","GSM8014813","GSM8014793","GSM8014795","GSM8014794","GSM8014805","GSM8014827","GSM8014826","GSM8014804","GSM8014829","GSM8014807","GSM8014806","GSM8014828","GSM8014809","GSM8014808","GSM8014821","GSM8014820","GSM8014823","GSM8014801","GSM8014800","GSM8014822","GSM8014803","GSM8014825","GSM8014802","GSM8014824","GSM8014816","GSM8014815","GSM8014818","GSM8014817","GSM8014819"],"GPL":["18573","19057"],"GSE":["253138"],"taxon":[" Mus musculus","Homo sapiens"],"PMID":["[39485844]"]}}