Phase Ib study of PRT543, an oral protein arginine methyltransferase 5 (PRMT5) inhibitor, in patients with advanced splicing factor-mutant myeloid malignancies
Jan Philipp Bewersdorf, Xiaoli Mi, Bin Lü, Andrew Kuykendall, David A. Sallman, Manish R. Patel, Don A. Stevens, Alexander Philipovskiy, Grerk Sutamtewagul, Lucia Masárová, Gina Keiffer, Amit Verma, Neha Bhagwat, Min Wang, Andrew S. Moore, Joseph Rager, Diane Heiser, Sunhee Ro, Wan‐Jen Hong, Omar Abdel‐Wahab, Eytan M. Stein
Abstract
Mutations in RNA splicing factor genes are common in patients with myelodysplastic neoplasms (MDS) and secondary acute myeloid leukemia (AML) [ 1 , 2 , 3 ]. Cells bearing these mutations have been shown to be preferentially sensitive to pharmacologic modulation of splicing compared to wild-type (WT) cells [ 4 , 5 ].
Topics & Concepts
Protein arginine methyltransferase 5MutantRNA splicingArginineSplicing factorCancer researchMyeloidMyeloid leukemiaAlternative splicingBiologyMethyltransferaseMedicineGeneticsMethylationGeneAmino acidGene isoformRNACancer-related gene regulationEpigenetics and DNA Methylation