Impact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Accelerated ageing of patients
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Patients with ET
45 patients with ET:
- 15 without thrombotic event (neither at diagnosis nor during follow-up)
- 15 with thrombotic events (thrombosis at diagnosis or within 2 years of diagnosis)
- 15 who progressed to myelofibrosis or AML during follow-up
干预措施: Assessment of the epigenetic age (Biological)
Patients with PV
45 patients with PV
- 15 without thrombotic event (neither at diagnosis nor during follow-up)
- 15 with thrombotic event (thrombosis at diagnosis or within 2 years of diagnosis)
- 15 who progressed to myelofibrosis or AML during follow-up
干预措施: Assessment of the epigenetic age (Biological)
Patients with PMF
20 patients with PMF:
- 10 without transformation into AML
- 10 patients who progressed to AML
干预措施: Assessment of the epigenetic age (Biological)
Patients without MPN
10 patients without MPN
干预措施: Assessment of the epigenetic age (Biological)
结局指标
主要结局
Accelerated ageing of patients
时间窗: At inclusion, up to 1 year after diagnosis
Accelerated ageing will be defined as an increased difference between the epigenetic age (calculated from DNA methylation data with the different molecular clocks described: DNAmAge, DNAmHannum, DNAmPhenoAge, DNAmSkinClock, DNAmGrimAge, intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration) and the chronological age
次要结局
- Additional somatic mutation(At inclusion, up to 1 year after diagnosis)
- Type of MPN (ET, PV or PMF) at diagnosis(At inclusion, up to 1 year after diagnosis)
- Transformation into secondary myelofibrosis or acute leukemia(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(Between 1 year before and 2 years after MPN diagnosis)
- Leukocytes(At inclusion, up to 1 year after diagnosis)
- Platelets(At inclusion, up to 1 year after diagnosis)
- Hemoglobin(At inclusion, up to 1 year after diagnosis)
- Granulocytes(At inclusion, up to 1 year after diagnosis)
- Monocytes(At inclusion, up to 1 year after diagnosis)
- Hematocrit(At inclusion, up to 1 year after diagnosis)