GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE253nnn/GSE253138/primaryOK200Transcriptomics Mus musculusHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE253138GEOGSEfalseA dual role for PSIP1/LEDGF in T-cell acute lymphoblastic leukemia [RNA-seq]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.2024/10/20GSE253138GSM8014797GSM8014830GSM8014796GSM8014799GSM8014810GSM8014832GSM8014831GSM8014798GSM8014834GSM8014812GSM8014833GSM8014811GSM8014814GSM8014813GSM8014793GSM8014795GSM8014794GSM8014805GSM8014827GSM8014826GSM8014804GSM8014829GSM8014807GSM8014806GSM8014828GSM8014809GSM8014808GSM8014821GSM8014820GSM8014823GSM8014801GSM8014800GSM8014822GSM8014803GSM8014825GSM8014802GSM8014824GSM8014816GSM8014815GSM8014818GSM8014817GSM80148191857319057253138 Mus musculusHomo sapiens[39485844]