Abstract:Increase in Tescalcin (TESC) gene expression and intracellular pH (pHi) have been associated with drug resistance in acute myeloid leukemia (AML). Tescalcin was shown to stabilize the membrane sodium/hydrogen exchanger (NHE1) that maintains a high pHi by H+ efflux in exchange for Na+. NHE1 has also been shown to be activated by PDGFR, PKC, calmodulin, p90-RSK and ROCK-RhoA, but their relevance to leukemogenesis and drug resistance in AML was unknown. We hypothesized that targeting NHE1 and its upstream activat… Show more
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