Article
Association of altered folylpolyglutamate synthetase pre-mRNA splicing with methotrexate unresponsiveness in early rheumatoid arthritis.
Rheumatology (Oxford, England) - 2 Mar 2021
Muller Ittai B, Lin Marry, Lems Willem F, Ter Wee Marieke M, Wojtuszkiewicz Anna, Nurmohamed Michael T, Cloos Jacqueline, Assaraf Yehuda G, Jansen Gerrit, de Jonge Robert
Abstract excerpt
OBJECTIVES: An efficient pharmacological response to MTX treatment in RA patients relies on the retention and accumulation of intracellular MTX-polyglutamates catalysed by the enzyme folylpolyglutamate synthetase (FPGS). We recently identified a partial retention of FPGS intron 8 (8PR) as a prominent splice variant conferring FPGS dysfunction and decreased MTX polyglutamylation in acute lymphoblastic leukaemia....
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