PRMT5 Inhibition Modulates E2F1 Methylation and Gene-Regulatory Networks Leading to Therapeutic Efficacy in JAK2V617F-Mutant MPN.

doi:10.1158/2159-8290.CD-20-0026

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Article

PRMT5 Inhibition Modulates E2F1 Methylation and Gene-Regulatory Networks Leading to Therapeutic Efficacy in JAK2V617F-Mutant MPN.

Cancer discovery - 1 Nov 2020

Pastore Friederike, Bhagwat Neha, Pastore Alessandro, Radzisheuskaya Aliaksandra, Karzai Abdul, Krishnan Aishwarya, Li Bing, Bowman Robert L, Xiao Wenbin, Viny Aaron D, Zouak Anouar, Park Young C, Cordner Keith B, Braunstein Stephanie, Maag Jesper L, Grego Alexander, Mehta Jaanvi, Wang Min, Lin Hong, Durham Benjamin H, Koche Richard P, Rampal Raajit K, Helin Kristian, Scherle Peggy, Vaddi Kris, Levine Ross L

Abstract excerpt

We investigated the role of PRMT5 in myeloproliferative neoplasm (MPN) pathogenesis and aimed to elucidate key PRMT5 targets contributing to MPN maintenance. PRMT5 is overexpressed in primary MPN cells, and PRMT5 inhibition potently reduced MPN cell proliferation ex vivo. PRMT5 inhibition was efficacious at reversing elevated hematocrit, leukocytosis, and splenomegaly in a model of JAK2V617F+ polycythemia vera...

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PMID: 32669286
DOI: 10.1158/2159-8290.CD-20-0026
PMCID: PMC7642059

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