Aberrant DNA methylation profiling of classic Philadelphia Negative Myeloproliferative Neoplasms

Since most DNA methylation studies in Classic Philadelphia-negative myeloproliferative neoplasms (MPNs) – polycythaemia vera (PV), essential thrombocythaemia (ET), and primary myelofibrosis (PMF) - have been performed on a gene-by-gene basis, a more comprehensive methylation profiling is needed to know the real implication of this alteration. In order to investigate the DNA methylation profile in chronic and transformed phase MPNs, we performed genome-wide DNA methylation arrays in 71 chronic (24 PV, 23 ET and 24 PMF) and 13 transformed MPNs. The three types of chronic MPNs showed the same aberrant DNA methylation pattern when compared to controls. Differentially methylated genes (DMG) were enriched in a gene network centered on the NF-κB pathway, indicating that they may be involved in the pathogenesis of these diseases. In the case of transformed MPNs we detected an increased number of DMGs with respect to chronic MPNs. Interestingly, these genes were enriched in a list of DMGs in primary AMLs and in a gene network centered around the IFN pathway. Further studies are clearly needed to elucidate the role of DMGs in MPNs, but our results suggest that this alteration plays an important role in the pathogenesis and transformation of MPNs and that modulation of these pathways would allow us to improve the quality of life of these patients. The methylation profile of 24 PBMCs samples from patients diagnosed with Policytemia Vera, 23 from Essential Thrombocythemia and 24 from primary myelofibrosis was assessed. We also included 13 secondary acute myeloid leukaemia (AML): 5 transformed PMF,4 transformed TE and 4 transformed PV. As reference,4 healthy donor PBMCs samples from whole peripheral blood and 4 PBMCs samples from bone marrow were used.