Study of Exon 12 Mutations in JAK2 Negative Myeloproliferative Disorder

The JAK2 (V617F) mutation involves the exon 14, which encodes a part of the JH2 auto-inhibitory domain of the JAK2 kinase. Scott and coworkers recently described mutations of JAK2 exon 12 in JAK2 (V617F)-negative patients with PV or idiopathic erythrocytosis. Their findings have been con-firmed by other studies. Using cellular models, it has been shown that exon 12 mutations can activate pathways associated with erythropoietin signaling, and in a murine model one of these mutations resulted in a myeloproliferative phenotype. In this work, we searched for the JAK2 (V617F) mutation in cases with myeloproliferative disorder (CML, ET, PRV and myelofibrosis) and the negative cases were investigated for exon 12 mutations. Methods: We searched for the JAK2 mutations in 40 cases of myeloproliferative patients and 10 patients with reactive erythrocytosis and thrombocytosis as a control, then all the 16 MPD cases with negative JAK2 were investigated for exon 12 mutations. Results: 24 cases showed Heterozygous positive of mutation JAK2, while all the cases of negative control showed negative, the 16 MPD cases negative for JAK2 mutation showed positive for Exon 12 mutation in five cases. Conclusions: JAK2 exon 12 mutations define a distinctive myeloproliferative syndrome that affects patients who currently are diagnosed as polycythemia vera or idiopathic erythrocytosis.