{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE190108"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"RNA-seq of murine spleocytes","description":"Aberrant expression of the T-cell lymphoma/leukemia 1A (TCL1A) oncogene is a hallmark of chronic lymphocytic leukemia (CLL) and is associated with aggressive disease features. A better understanding of functional networks around TCL1A is required to develop new treatment approaches in CLL. Here, we identify the epigenetic modifying lysine-specific demethylase KDM1A as a nuclear interaction partner of the TCL1A protein in CLL B-cells. Interestingly, binding to TCL1A increased KDM1A?s demethylase activity. Moreover, higher KDM1A expression correlated with adverse clinical characteristics and shorter progression-free survival in CLL. Kdm1a knockdown (Kdm1a-KD) reduced leukemic burden and prolonged overall survival in a CLL mouse model accompanied by upregulation of p53 and pro-apoptotic pathways. RNA-seq analysis of differentially expressed genes upon Kdm1a-KD suggests that Kdm1a might act as a transcriptional repressor. In addition, ChIP experiments demonstrated an altered modification of H3K4me3 in Kdm1a-KD mice. Moreover, KDM1A expression in the microenvironmental had an impact on its support for CLL progression. In line, KDM1A inhibition by the pharmacologic compound C12 induced apoptosis and affected H3K4/9 target methylation levels in B-cell lines and CLL samples. Overall, we found a relevant pathogenetic role of KDM1A as a pro-oncogenic marker in CLL cells and their microenvironment. This provides a novel treatment rationale for targeting KDM1A in CLL.","dates":{"publication":"2023/05/02"},"accession":"GSE190108","cross_references":{"GSM":["GSM5714251","GSM5714252","GSM5714253","GSM5714254","GSM5714255","GSM5714256","GSM5714257","GSM5714258"],"GPL":["24247"],"SRA":["SRP349125"],"GSE":["190108"],"taxon":["Mus musculus"]}}