Myelodysplastic Syndromes with Myelofibrosis May Be a Target for the JAK2 V617F Tyrosine Kinase Mutation.

The JAK V617F tyrosine kinase mutation is responsible for development of the disease in chronic myeloproliferative disorders, including myelofibrosis (MF). Since MF is associated with various hematologic diseases as a terminal hematologic condition and is an important issue in managing patients, we searched for the V617F mutation in primary and secondary MF in various hematologic diseases using the sequence-specific primer-single molecule fluorescence detection assay (SSP-SMFD). Of the MF patients associated with acute myeloid leukemia and (n = 3), lymphoma (n = 3), and chronic myeloid leukemia (n = 3), none of them showed the mutation at the time of the diagnosis of MF. Approximately 40% of essential thrombocythemia (ET: n = 16) and primary MF (n = 4) showed the JAK2 V617F mutation, whereas 6 of 8 patients with polycythemia vera showed the mutation. Of note is that 2 of 6 patients with myelodysplastic syndromes (MDS) terminating in MF showed the mutation, while no MDS patient without MF (MDS: n = 3) had the JAK2 V617F mutation. Our study clearly demonstrated that MF in MDS patients is sometimes associated with JAK2 V617F mutation, while other underlying diseases developing MF may involve other pathways. Moreover, it permits speculation that clonal evolution in some MDS patients with the JAK2 V617F tyrosine kinase mutation may be responsible for secondary MF.