Analysis of signal transduction of Polycythemia vera-associated JAK2 V617F mutant

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The constitutively activated mutation of tyrosine kinase JAK2 (V617F) is found in the majority of the patients with polycythemia vera. We found that JAK2 mutant induces transformation through aberrant activation of STAT5. Interestingly, it was found that the expression of Aurora kinase A and activation of Akt were significantly induced by JAK2 mutant. We showed that Aurora kinase A was critical for JAK2 mutant-induced resistance to cisplatin-induced DNA damage. Furthermore, we clarified that Akt activation induced the downregulation of anti-apoptotic proteins, leading to anti-apoptotic activity.