Molecular pathogenesis of abnormal kpm (Lats2) expression in leukemia

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Kpm (Lats2) is a serine-threonine kinase that is one of the core components of the Hippo signaling pathway. We measured expression levels of kpm (Lats2) in various leukemias and found that expression of kpm was downregulated in refractory leukemias. Knockdown of kpm (Lats2) rendered leukemic cells resistant to anti-cancer drugs. We demonstrated that stabilization of nuclear p73 after DNA damage and subsequent induction of PUMA and p21 require phosphorylation of YAP2 at serine-127 by Kpm (Lats2). Thus, downregulation of kpm (Lats2) seems to be one of the mechanisms for chemoresistance.