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

University Hospital of Bordeaux

Status: Enrolling

Conditions: Myeloproliferative Neoplasm

Treatments: Biological: Assessment of the epigenetic age

Study type: Observational

Funder types: Other

Identifiers

NCT06022328

CHUBX 2023/15

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

120 participants in 4 patient groups

Patients with ET

Description:

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

Treatment:

Biological: Assessment of the epigenetic age

Patients with PV

Description:

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

Treatment:

Biological: Assessment of the epigenetic age

Patients with PMF

Description:

20 patients with PMF: * 10 without transformation into AML * 10 patients who progressed to AML

Treatment:

Biological: Assessment of the epigenetic age

Patients without MPN

Description:

10 patients without MPN

Treatment:

Biological: Assessment of the epigenetic age