Infrequent hypermethylation of WIF-1 promoter in BCR/ABL-negative myeloproliferative disorders.

OBJECTIVE

The Wnt/β;-catenin signaling pathway is important in the pathogenesis of hematological malignancies. Wnt inhibitory factor-1 (WIF-1) is a negative regulator of Wnt signaling that is frequently downregulated by hypermethylation of the WIF-1 promoter in acute promyelocytic leukemia (APL) and other malignancies. On the other hand, an acquired mutation in JAK2 tyrosine kinase involving a V617F amino-acid substitution shows a strong association with the pathogenesis of BCR/ABL-negative MPD. This is the first study to examine the relationship between WIF-1 methylation and the existence of JAK2V617F mutation in the pathogenesis of BCR/ABL-negative myeloproliferative disorders (MPD) including polycythemia vera, essential thrombocythemia, idiopathic myelofibrosis, and chronic myeloproliferative disease, unclassifiable.

METHODS

We evaluated 49 newly diagnosed and previously treated patients with MPD in chronic phase. Bone marrow (BM) mononuclear cells, when available, or PB mononuclear cells of patients were used for the analysis. The mutation status of JAK2 was analyzed using sequencing analysis. The methylation status of the WIF-1 promoter was analyzed by methylation-specific polymerase chain reaction (MSP).

RESULTS

The JAK2V617F mutation was found in 23/49 patients (46.9%) with BCR/ABL-negative MPD, while WIF-1 methylation was detected in 1/49 patients (2.0%).

CONCLUSION

WIF-1 is infrequently methylated in BCR/ABL-negative MPD.