GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE190nnn/GSE190108/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE190108GEOGSEfalseRNA-seq of murine spleocytesAberrant 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.2023/05/02GSE190108GSM5714251GSM5714252GSM5714253GSM5714254GSM5714255GSM5714256GSM5714257GSM571425824247SRP349125190108Mus musculus