Heart and Blood Diseases

All Conditions

Blood and Lymph Conditions

Rare Diseases

Thrombosis

Myeloproliferative Disorders

Embolism

Embolism and Thrombosis

Vascular Diseases

Bone Marrow Diseases

Hematologic Diseases

Chronic Myeloproliferative Disorders

For the main objective, the cohort will be composed of PV and ET patients, some with a history of thrombosis and some without any history of thrombosis. A comparison will also be performed between patients with different MPN (PV or ET) and different driver mutation (JAK2V617F, JAK2 exon 12, CALR, MPL or absence of such mutations)

For all the patients included, a specific blood sampling will be performed in addition to the classical evaluations that are performed in routine practice

1 additional tube of blood

Olivier MANSIER

Chloé JAMES

Clémence MEDIAVILLA

Pierre DUFFAU

Jean-François VIALLARD

Etienne GABRIEL

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.

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

Patients wil be classified as having a history of thrombosis if they had a deep vein thrombosis, pulmonary embolism, splanchnic thombosis or any other significant thrombosis. Tinnitus, vertigo, headaches, erythromelalgia as well as superficial vein thrombosis will not be considered as thrombotic events

The proportion of CD16+ monocytes will be assessed in PV and ET patients, and compared between patients with a history of thrombosis and those without any history of thrombosis

The different sub-populations will be defined according to the expression profile of CD14 and CD16, defining classical monocytes (CD14++CD16-), non-classical monocytes (CD14loCD16++) and intermediate monocytes (CD14+CD16+). The proportion of these sub-populations will be assessed in PV and ET patients, and compared between patients with a history of thrombosis and those without any history of thrombosis

The count (G/L) of the different monocytes sub-populations, ie CD16+ monocytes, classical monocytes (CD14++CD16-), non-classical monocytes (CD14loCD16++) and intermediate monocytes (CD14+CD16+) will be assessed in PV and ET patients, and compared between patients with a history of thrombosis and those without any history of thrombosis

The type of MPN will be determined according to the WHO criteria as PV or ET. Patients will be classified as PV if they have an increased hemoglobin level (\>16.5g/dL for men, \>16g/dL for women), hematocrit (\>49% for men, \>48% for women), or red cell mass (\>125% of theoretical value), together with a mutation in the JAK2 gene (JAK2V617F or exon 12), and a subnormal EPO level. If performed, bone marrow biopsy should be in favor of an MPN.

Patients will be classified as ET if they present a thrombocytosis \> 450 G/L, with a detectable mutation in JAK2, CALR or MPL. If performed, bone marrow biopsy should be in favor of an MPN.

At diagnosis, a driver mutation is searched in MPN patients. We will classify patients in different groups depending on whether they carry the JAK2V617F mutation, a mutation in JAK2 exon 12, a mutation in CALR exon 9, a mutation in MPL exon 10 or any of these mutations (triple negative category). We will thus distinguish 5 groups of patients: "JAK2V617F", "JAK2 exon 12", "CALR exon 9", "MPL exon 10", "triple negative". The proportion of monocytes sub-populations will be compared between these different groups of patients

A correlation between the hemoglobin level (g/dL) and monocytes sub-populations proportion will be searched

A correlation between the platelets level (G/L) and monocytes sub-populations proportion will be searched

A correlation between the leukocytes level (G/L) and monocytes sub-populations proportion will be searched

A correlation between the proportion or count of monocytes sub-populations and thrombosis risk factors will be searched. These include age\>60 years, history of thrombosis, tobaccoe use (actual or stopped for les than 3 years), hyperLDLcholesterol level (LDL-Cholesterol \> 3,36 mmol/L), hypoHDLcholesterol level (HDL \< 1,03 mmol/L in men or \< 1,29 mmol/L in women), diabetes (glycemia \> 6,93 mmol/L), high blood pressure (\> 140/90 mmHg)

Spots Global Cancer Trial Database for 1 additional tube of blood