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Chromatin-modifying enzymes, and specifically the protein arginine methyltransferases (PRMTs), have emerged as important targets in cancer. Here, we investigated the role of CARM1 in normal and malignant hematopoiesis. Using conditional knockout mice, we show that loss of CARM1 has little effect on normal hematopoiesis. Strikingly, knockout of Carm1 abrogates both the initiation and maintenance of acute myeloid leukemia (AML) driven by oncogenic transcription factors. We show that CARM1 knockdown impairs cell-cycle progression, promotes myeloid differentiation, and ultimately induces apoptosis. Finally, we utilize a selective, small-molecule inhibitor of CARM1 to validate the efficacy of CARM1 inhibition in leukemia cells in vitro and in vivo. Collectively, this work suggests that targeting CARM1 may be an effective therapeutic strategy for AML.
Pubmed ID: 29894694 RIS Download
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Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
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View all literature mentionsCell line AML14 [Human leukemia] is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line TF-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SET-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MV4-11 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NOMO-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U-937 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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