<prompt> Methotrexate resistance is due to:Depletion of folateOverproduction of DHFRaseOverproduction of thymidylate kinaseDecreased DHFRase  <response>: Ans. B Overproduction of DHFRaseRef: Goodman and Gilman, 11the p1336Mechanisms of methotrexate resistanceImpaired transport of methotrexate into cellsProduction of altered forms of DHFR that have decreased affinity for the inhibitorIncreased concentrations of intracellular DHFR through gene amplification or altered gene regulationDecreased ability to synthesize methotrexate polyglutamatesIncreased expression of a drug efflux transporter, of the MRP multidrug resistance protein class. 