Role of Monocytes Sub-populations in Thrombosis Associated With Myeloproliferative Neoplasms (MonSThr)

Role of Monocytes Sub-populations in Thrombosis Associated With Myeloproliferative Neoplasms (MonSThr)

Myeloproliferative neoplasms (MPN) are hematological malignancies associated with a major risk of thrombosis. Monocytes are hematopoietic cells with a central role in thrombosis. An activation of monocytes has been demonstrated in MPN patients. However, their study in MPN and their thrombotic complications has never been performed. In this study, we aim to evaluate the association between monocytes sub-populations and thrombotic risk in MPN patients.

Myeloproliferative Neoplasms (MPN) are hematological malignancies characterized by an increased risk of thrombosis, in particular in Polycythemia Vera (PV) and Essential Thrombocythemia (ET). Predicting the risk of thrombosis in PV and ET patients helps at determining their care (use of antiaggregant and cytoreductive therapies), but relies only on limited clinical and biological criteria (age over 60 years, history of thrombosis, presence of the JAK2V617F mutation, presence of cardiovascular risk factors). Monocytes sub-populations could represent a new biomarker of thrombotic risk in PV and ET patients. Indeed, it has been shown that monocytes are activated and exhibit pro-thrombotic properties in MPN patients, especially those with a history of thrombosis. Some studies have suggested the CD16+ monocytes (intermediate and non-classical monocytes) are associated with an increased risk of arterial thrombosis. Because these monocytes are observed in inflammatory contexts, and because MPN are associated with a chronic inflammation, MPN could be associated with an increase of the proportion or the absolute count of CD16+ monocytes that could be involved in thrombotic complications observed in PV and ET patients.

In this project, an association between the proportion of CD16+ monocytes and thrombosis in PV and ET patients will be searched. Monocytes sub-populations will be studied in PV and ET patients at diagnosis as described by Selimoglu-Buet et al.1 The proportion of CD16+ (intermediate + non-classical) monocytes will be compared between patients presenting with a history of thrombosis and those without any history of thrombosis. The association between the absolute count and the proportion of CD16+, intermediate and non-classical monocytes and the occurrence of thrombosis before diagnosis, the MPN phenotype, the driver mutation, the allelic burden, the clinico-biological presentation and the existence of an inflammatory state will also be evaluated. Due to the low frequency and the high latency of thrombosis reoccurrence, patients' samples only at diagnosis (or during the year after diagnosis) will be analyzed and an association with a history of thrombosis will be made.

Inclusion Criteria:

• Adults patients (age ≥ 18 years)
• Inclusion at diagnosis or during the year following the diagnosis of PV or ET (2016 WHO criteria except bone marrow biopsy that is optional in the presence of a marker of clonality)
• Subject registered with a social security scheme
• Written informed consent obtained

Exclusion Criteria:

• Patients with cytoreductive treatment (hydroxyurea, anagrelide, interferon, ruxolitinib) at the time of blood sampling

• Chronic inflammatory disease (cancer, vasculitis, rheumatism, hepato-gastro-intestinal diseases).

• Long term anti-inflammatory treatments:

  • Corticoids
  • Nonsteroidal anti-inflammatory drugs
  • Aspirin (> 325 mg per day)
  • Cyclo-oxygenase II inhibitors

• Persons under judicial safeguards, trustee or curatorship

• Person unable to give her consent

• Non-cooperative person

• Exclusion period after another clinical study or participation to another clinical study in the 30 days before inclusion