Impact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC)

Overview

Myeloproliferative Neoplasms (MPN) are hematological malignancies characterized by the excessive production of myeloid cells. MPN can be complicated by thrombosis and evolution into more aggressive diseases (myelofibrosis and acute leukemia). Aging remains the principal factor determining patients' survival in MPN. In recent years, DNA methylation has appeared as a mean to measure aging via the development of epigenetic clocks that have also been associated with the occurrence of thrombosis and cancer. The epiC project aims at determining epigenetic age of MPN patients and search for an association between this parameter and thrombotic/hematological complications.

Myeloproliferative Neoplasia (MPN) are hematological malignancies characterized by the excessive production of myeloid cells. They include Essential Thrombocythemia (ET), Polycythemia Vera (VP) and Primary Myelofibrosis (PMF). Thrombosis are the most frequent complications and are largely responsible for the morbidity and mortality observed in ET and PV patients. The most feared complications are hematological transformations (into myelofibrosis for PV and ET, into acute myeloid leukemia for PV, ET and PMF). The prognostic assessment of MPN patients is mainly based on clinical data. Although recent studies have shown that certain mutations are associated with a poorer prognosis, age remains the main risk factor affecting survival in MPN patients. Recent studies have shown that DNA methylation can be used to determine an "epigenetic age". Interestingly, this epigenetic age is associated with the development of cardiovascular disease and cancer. In this project, the epigenetic age of MPN patients will be determined by studying the DNA methylation at diagnosis using the Infinium Human MethylationEPIC kit (Illumina). Epigenetic age will be determined with the most commonly used epigenetic clocks (DNAmAge, DNAmHannum, DNAmPhenoAge, DNAmSkinClock, DNAmGrimAge, intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration). It will be searched for an association between accelerated epigenetic aging (as assessed by the difference between epigenetic age and chronological age) and the type of MPN, the clinical and biological presentation at diagnosis (including the mutational profile of patients) and the occurrence of thrombosis and hematological evolution into myelofibrosis and/or acute leukemia.