Functional and Phenotypic Characterization of Monocytes in Myeloproliferative Syndromes

NCT ID: NCT06361641

Last Updated: 2025-12-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-29
• Study Completion Date: 2028-10-19

Brief Summary

Prospective study for functional and phenotypic characterization of monocytes in philadelphia-negative myeloproliferative neoplasms

Detailed Description

Philadelphia-negative myeloproliferative neoplasms (MPN) are clonal disorders of the hematopoietic stem cell characterized by an excessive production of mature myeloid cells. MPNs are characterized by the presence of somatic gain-of-function mutations present in more than 80% of cases and affecting JAK2, CALR or MPL genes. These mutations lead to a constitutive activation of the JAK-STAT signaling pathway at the origin of cell proliferation.

MPN include polycythemia vera (PV), essential thrombocythemia (ET), prefibrotic primary myelofibrosis (pre-PMF), and primary myelofibrosis (PMF). Despite the classification of MPNs into distinct subtypes based on clinical and pathological features, the precise mechanisms underlying the phenotypic diversity within these disorders remain poorly understood. One aspect that has received limited attention is the role of monocytes and macrophages, key components of the innate immune system, in MPN pathogenesis.

Monocytes, circulating precursors of tissue-resident macrophages, play essential roles in inflammation, immune surveillance, and tissue repair. Upon recruitment to tissues, monocytes differentiate into macrophages with diverse phenotypes and functions influenced by local microenvironmental cues. Macrophages, in turn, exhibit a spectrum of activation states ranging from pro-inflammatory (M1) to anti-inflammatory or pro-repair (M2), with implications for various physiological and pathological processes. Recent studies have implicated monocytes and macrophages in the pathogenesis of MPNs. Circulating monocytes in MPN patients display altered functional characteristics, including dysregulated cytokine production and enhanced fibrotic potential. Additionally, monocytosis, an elevated monocyte count, has been identified as an adverse prognostic factor in MPNs, particularly in PMF.

Based on these observations, investigator propose that monocytes and macrophages contribute to the phenotypic expression of MPNs and that distinct phenotypic and functional signatures of these cells may be associated with different MPN subtypes. By leveraging available techniques for genetic and functional analysis, study team aims to elucidate the role of monocytes and macrophages in MPN pathogenesis and identify potential biomarkers associated with disease phenotype and prognosis. Through comprehensive characterization of these immune cell populations, investigator seek to gain insights into the underlying mechanisms driving the heterogeneity of MPNs and identify novel therapeutic targets for precision medicine approaches.

Conditions

Myeloproliferative Neoplasm; Polycythemia Vera; Essential Thrombocythemia; Primary Myelofibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Phemop Cohort

Group Type: EXPERIMENTAL

Monocytes signatures in myeloproliferative neoplasms at diagnosis

Intervention Type: DIAGNOSTIC_TEST

The monocytes signatures will be perform from a peripheral blood sample. The signature will be derived from (i) surface marker expression, (ii) cytokines profiles, (iii) genes expression.

Interventions

Monocytes signatures in myeloproliferative neoplasms at diagnosis

The monocytes signatures will be perform from a peripheral blood sample. The signature will be derived from (i) surface marker expression, (ii) cytokines profiles, (iii) genes expression.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Diagnosis of PV, ET, pre-myelofibrosis or primary myelofibrosis according to WHO 2022 criteria (including BOM for ET, premyelofibrosis and primary myelofibrosis)
• Patient who has not received treatment specific to hemopathy at the time of sampling
• Obtaining the signature of consent to participate in the study
• Patient having consented to be included in the "Malignant Hemopathy" collection of Angers University Hospital and in FIMBANK database

Exclusion Criteria

• Person not affiliated to a social security scheme or beneficiary of such a scheme
• Patient with another hemopathy or another active cancer at the time of diagnosis
• Minor patient at diagnosis (< 18 years old)
• Patient not capable or without agreement from the guardian or legal representative

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Angers

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Agathe GOUBAND, PharmD

Role: PRINCIPAL_INVESTIGATOR

University Hospital

Locations

GOUBAND Agathe

Angers, Maine et Loire, France

Site Status: RECRUITING

BESCOND Charles

Cholet, Maine et Loire, France

Site Status: NOT_YET_RECRUITING

TRUCHAN-GRACZYK Malgorzata

Saumur, Maine et Loire, France

Site Status: NOT_YET_RECRUITING

Countries

France

Central Contacts

Agathe GOUBAND, PharmD

Role: CONTACT

Agathe.Gouband@chu-angers.fr

02 41 35 55 96 ext. 33

UH Angers DRCI

Role: CONTACT

DRCI-Promotion-Interne@chu-angers.fr

+ 33 2 41 35 54 96 ext. 33

Facility Contacts

Agathe GOUBAND, PharmD

Role: primary

Agathe.Gouband@chu-angers.fr

02 41 35 55 96 ext. 33

Damien LUQUE PAZ, PharmD

Role: backup

Damien.LuquePaz@chu-angers.fr

02 41 35 53 53 ext. 33

Charles BESCOND, MD

Role: primary

charles.bescond@ch-cholet.fr

0241355880

Malgorzata TRUCHAN-GRACZYK, MD

Role: primary

matruchan@ch-saumur.fr

0241533544 ext. 33

Other Identifiers

AO2721-44

Identifier Type: OTHER

Identifier Source: secondary_id

49RC23_0259

Identifier Type: -

Identifier Source: org_study_id