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

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.

Study Overview

• Status: Recruiting
• Conditions: Myeloproliferative Neoplasm
• Intervention / Treatment: Biological: Assessment of the epigenetic age

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.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Olivier MANSIER; Email: olivier.mansier@chu-bordeaux.fr

Study Locations

• France
  • Bordeaux, France
    • Recruiting
    • CHU de Bordeaux, Service Hématologie Biologique
    • Contact: Olivier MANSIER; Email: olivier.mansier@chu-bordeaux.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with Myeloproliferative Neoplasia (MPN) : Essential Thrombocythemia (ET), Polycythemia Vera (VP) or Primary Myelofibrosis (PMF)

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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	Biological: Assessment of the epigenetic age; Retrospective assessment of the epigenetic age on DNA samples obtained at diagnosis
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	Biological: Assessment of the epigenetic age; Retrospective assessment of the epigenetic age on DNA samples obtained at diagnosis
Patients with PMF; 20 patients with PMF: 10 without transformation into AML; 10 patients who progressed to AML	Biological: Assessment of the epigenetic age; Retrospective assessment of the epigenetic age on DNA samples obtained at diagnosis
Patients without MPN; 10 patients without MPN	Biological: Assessment of the epigenetic age; Retrospective assessment of the epigenetic age on DNA samples obtained at diagnosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accelerated ageing of patients	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	At inclusion, up to 1 year after diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type of MPN (ET, PV or PMF) at diagnosis	We will study patients with a diagnosis of ET, PV or PMF as defined by the WHO classification of hematological malignancies	At inclusion, up to 1 year after diagnosis
Transformation into secondary myelofibrosis or acute leukemia	Evolution toward secondary myelofibrosis or acute leukemia will be defined according to the WHO classification of hematological malignancies	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	Occurrence of myocardial infarction, ischemic stroke, deep vein thrombosis, pulmonary embolism, splanchnic thrombosis or any other significant thrombosis. Tinnitus, vertigo, headaches, erythromelalgia as well as superficial vein thrombosis will not be considered as thrombotic events	Between 1 year before and 2 years after MPN diagnosis
Leukocytes	Leukocytes level on blood count in G/L	At inclusion, up to 1 year after diagnosis
Platelets	Platelet level on blood count in G/L	At inclusion, up to 1 year after diagnosis
Granulocytes	Granulocytes level on blood count in G/L	At inclusion, up to 1 year after diagnosis
Monocytes	Monocytes level on blood count in G/L	At inclusion, up to 1 year after diagnosis
Hemoglobin	Hemoglobin level on blood count in g/dL	At inclusion, up to 1 year after diagnosis
Hematocrit	Hematocrit level on blood count in %	At inclusion, up to 1 year after diagnosis
Additional somatic mutation	In up to 50% of MPN patients, genetic variants can be detected in genes such as DNMT3A, TET2, ASXL1, SRSF2, SF3B1, U2AF1, EZH2 or TP53. We will determine which somatic genetic variant is detected by high throughput sequencing	At inclusion, up to 1 year after diagnosis

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: August 28, 2023
• First Posted (Actual): September 1, 2023

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Myelofibrosis; Leukemia; Thrombosis; Myeloproliferative Neoplasm; Epigenetic age
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Neoplasms; Myeloproliferative Disorders
• Other Study ID Numbers: CHUBX 2023/15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No