Jak2 V617f Mutation: a Marker for Cml Progression?

Treatment with Imatinib mesylate leads to molecular remission in majority of Philadelphia chromosome (Ph) positive Chronic Myeloid Leukemia (CML) cases. However, sometimes persistent anemia or evolving myelofibrosis is observed due to a co-existing Ph negative chronic Myelo Proliferative Disorder (CMPD) clone. Polycythemia vera (PV) is the most common Myelo Proliferative Disorder (MPD) coexisting with CML and 80% of cases with PV showed JAK2V617F mutation. Janus kinase2 (JAK2) gene plays a major role in maintaining BCR-ABL stability as BCR-ABL exerts its oncogenic signaling through the involvement of Jak2 phosphorylation. JAK2V617F mutation results in hyperactivation of JAK2 gene and had been implicated in several hematologic malignancies. In our study, the JAK2V617F mutation was detected through Amplification Refractory Mutation Detection-Polymerase Chain Reaction (ARMS-PCR) method in 6 out of 480 CML cases. None of the 350 controls showed this mutation. Patients with JAK2 mutation except for one failed to show complete molecular remission despite the prolonged treatment with Imatinib. The results suggested that JAK2 V617F mutation could be a marker for CML progression and JAK2 could serve as alternative drug target in Imatinib resistant CML cases with persistent myelofibrosis.