Impact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Assessment of the epigenetic age.
- Who it may be relevant to
- Registry conditions: Myeloproliferative Neoplasm. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
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.
Detailed description
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.
Interventions
- Biological Assessment of the epigenetic age
Retrospective assessment of the epigenetic age on DNA samples obtained at diagnosis
Primary outcome measures
- Accelerated ageing of patients [Time frame: At inclusion, up to 1 year after diagnosis]
Secondary outcome measures (10)
- Type of MPN (ET, PV or PMF) at diagnosis [Time frame: At inclusion, up to 1 year after diagnosis]
- Transformation into secondary myelofibrosis or acute leukemia [Time frame: From date of inclusion until documentation of the event, assessed up to 5 years]
- Occurrence of thrombosis prior to diagnosis or during follow-up of the disease [Time frame: Between 1 year before and 2 years after MPN diagnosis]
- Leukocytes [Time frame: At inclusion, up to 1 year after diagnosis]
- Platelets [Time frame: At inclusion, up to 1 year after diagnosis]
- Granulocytes [Time frame: At inclusion, up to 1 year after diagnosis]
- Monocytes [Time frame: At inclusion, up to 1 year after diagnosis]
- Hemoglobin [Time frame: At inclusion, up to 1 year after diagnosis]
- Hematocrit [Time frame: At inclusion, up to 1 year after diagnosis]
- Additional somatic mutation [Time frame: At inclusion, up to 1 year after diagnosis]
Eligibility criteria
Inclusion criteria
For the 110 patients with MPN:
- Patients with PV, ET or PMF
- DNA extracted from purified granulocytes at time of diagnosis
- No treatment likely to impact DNA methylation (chemotherapy, immunosuppressants in particular)
For the 10 subjects without MPN:
- Absence of hematological malignancy
- Search for JAK2V617F mutation in the context of reactive thrombocytosis or secondary polycythemia
- Absence of treatment likely to impact DNA methylation (chemotherapy, immunosuppressants in particular)
Exclusion criteria
For the 110 patients with MPN:
- Patients without PV, ET or PMF
- Patients without purified granulocytes DNA available at time of diagnosis
- Patients treated by cytoreductive drug, demethylating agent, chemotherapy or immunosuppressive therapy at the time of DNA sampling
- Patients with less than 2 years' follow-up
For the 10 subjects in NMP :
- Patients with hematological malignancy and/or solid cancer
- Patients treated by cytoreductive drug, demethylating agent, chemotherapy or immunosuppressive therapy at the time of DNA sampling
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
France · 1 center
- CHU de Bordeaux, service Hématologie Biologique — Bordeaux
Identifiers
NCT: NCT06022328 · CHUBX 2023/15