Genetic deletion or small-molecule inhibition of the arginine methyltransferase PRMT5 exhibit anti-tumoral activity in mouse models of MLL-rearranged AML.

ABSTRACT: The hematological malignancies classified as mixed lineage leukemias (MLL) harbor fusions of the MLL1 gene to partners that are members of transcriptional elongation complexes. MLL-rearranged leukemias are associated with extremely poor prognosis, and response to conventional therapies and efforts to identify molecular targets are urgently needed. Using mouse models of MLL-rearranged acute myeloid leukemia, here we show that genetic inactivation or small-molecule inhibition of the protein arginine methyltransferase PRMT5 exhibit anti-tumoral activity in MLL-fusion protein-driven transformation. Genome-wide transcriptional analysis revealed that inhibition of PRMT5 methyltransferase activity overrides the differentiation block in leukemia cells without affecting the expression of MLL-fusion

SUBMITTER: Kaushik S 

PROVIDER: S-EPMC5865447 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature