Methylation of cyclin-dependent kinase inhibitors, XAF1, JUNB, CDH13 and soluble Wnt inhibitors in essential thrombocythaemia.

BACKGROUND

Methylation of genes regulating cell-cycle check-point (INK4 cyclin-dependent kinase inhibitors), apoptosis (XAF1), adhesion (CDH13), JUNB and Wnt signalling (soluble Wnt inhibitors) has been implicated in pathogenesis of haematological and epithelial cancers.

METHOD: The authors studied the methylation status of CDKN2A, CDKN2B, XAF1, CDH13, JUNB and a panel of soluble Wnt inhibitors including WIF1, DKK3, APC, SFRP1, SFRP2, SFRP4 and SFRP5 by methylation-specific PCR in 31 bone marrow and 21 peripheral blood samples of patients with essential thrombocythaemia.

RESULTS AND DISCUSSION: There was no evidence of hypermethylation of all these genes in both the BM and PB samples. Therefore, in contrast to myeloid leukaemias, methylation of these genes regulating the cell cycle, apoptosis, adhesion and Wnt signalling does not play an important role in the pathogenesis of myeloproliferative diseases. Whether differential methylation may occur in the progenitor or mature blood cell compartments remains to be verified. Our study contributes to the literature on methylation in chronic myeloproliferatve diseases.