PRMT1-mediated FLT3 arginine methylation promotes maintenance of FLT3-ITD⁺ acute myeloid leukemia.

ABSTRACT: The presence of FMS-like receptor tyrosine kinase-3 internal tandem duplication (FLT3-ITD) mutations in patients with acute myeloid leukemia (AML) is associated with poor clinical outcome. FLT3 tyrosine kinase inhibitors (TKIs), although effective in kinase ablation, do not eliminate primitive FLT3-ITD⁺ leukemia cells, which are potential sources of relapse. Thus, understanding the mechanisms underlying FLT3-ITD⁺ AML cell persistence is essential to devise future AML therapies. Here, we show that expression of protein arginine methyltransferase 1 (PRMT1), the primary type I arginine methyltransferase, is increased significantly in AML cells relative to normal hematopoietic cells. Genome-wide analysis, coimmunoprecipitation assay, and PRMT1-knockout mouse studie

SUBMITTER: He X 

PROVIDER: S-EPMC6688430 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature