Clinical trial NCT06022328: Impact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC)
Official title: Impact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Myeloproliferative Neoplasm
Keywords: Myeloproliferative Neoplasm
Epigenetic age
Thrombosis
Myelofibrosis
Leukemia
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2023-09-01
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with Myeloproliferative Neoplasia (MPN) : Essential Thrombocythemia (ET), Polycythemia Vera (VP) or Primary Myelofibrosis (PMF)

Brief summary: 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.

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

Primary outcomes:
measure: Accelerated ageing of patients
timeFrame: At inclusion, up to 1 year after diagnosis
Secondary outcomes:
measure: Type of MPN (ET, PV or PMF) at diagnosis
timeFrame: At inclusion, up to 1 year after diagnosis
measure: Transformation into secondary myelofibrosis or acute leukemia
timeFrame: From date of inclusion until documentation of the event, assessed up to 5 years
measure: Occurrence of thrombosis prior to diagnosis or during follow-up of the disease
timeFrame: Between 1 year before and 2 years after MPN diagnosis
measure: Leukocytes
timeFrame: At inclusion, up to 1 year after diagnosis
measure: Platelets
timeFrame: At inclusion, up to 1 year after diagnosis
measure: Granulocytes
timeFrame: At inclusion, up to 1 year after diagnosis
measure: Monocytes
timeFrame: At inclusion, up to 1 year after diagnosis
measure: Hemoglobin
timeFrame: At inclusion, up to 1 year after diagnosis
measure: Hematocrit
timeFrame: At inclusion, up to 1 year after diagnosis
measure: Additional somatic mutation
timeFrame: At inclusion, up to 1 year after diagnosis
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux, service Hématologie Biologique
Study officials:
References: