Background and objectives: The role of the Janus kinase 2 V617F (JAK2(V617F)) mutation in the pathogenesis of the various BCR-ABL1-negative myeloproliferative neoplasms (MPNs) remains unclear. Its significance in leukemic transformation is a matter of even greater controversy. The aim of this study was to evaluate both the JAK2(V617F) mutational status of the rare cases in which blast crisis occurred in our institution and the response after intensive treatment.
Materials and methods: Between 1999 and 2009, 778 patients received diagnoses of BCR-ABL1-negative MPNs in our center (395 polycythemia vera, 329 essential thrombocythemia, and 45 primary myelofibrosis cases, as well as 9 MPN cases not otherwise classifiable). Of these patients, 7 developed leukemic transformation. The genotyping of the JAK2(V617F) mutation was performed by the amplification-refractory mutation system.
Results: Six of the 7 patients were tested for JAK2(V617F) in the chronic phase of their disease, and 3 of these patients were positive for JAK2(V617F). These patients, 2 with polycythemia vera and 1 with essential thrombocythemia, also harbored JAK2(V617F) in the heterozygous state during blast crisis and even after intensive treatment in one of these patients. The other cases that evolved to blast crisis did not harbor the JAK2(V617F) mutation before and after transformation. All 7 patients died despite conventional or supportive treatment.
Conclusions: The transformation of MPNs into acute leukemia is by itself a very rare phenomenon, and so is the persistence of the JAK2(V617F) mutation after blast crisis. In our series, all JAK2(V617F)-positive patients remained positive for this mutation after leukemic transformation, although in the heterozygous state, suggesting that JAK2(V617F) is not essential for transformation in these cases. The fact that all JAK2(V617F)-negative cases remained negative after blast crisis reinforces the theory that other molecular event(s) may play a role in the clonal heterogeneity of MPNs. Owing to the poor outcome of acute myeloid leukemia secondary to MPN, patients should be included in clinical trials of the novel JAK2 inhibitors.