Functional and Phenotypic Characterization of Monocytes in Myeloproliferative Syndromes (PHEMOP)

U

University Hospital, Angers

Status

Not yet enrolling

Conditions

Polycythemia Vera
Primary Myelofibrosis
Myeloproliferative Neoplasm
Essential Thrombocythemia

Treatments

Diagnostic Test: Monocytes signatures in myeloproliferative neoplasms at diagnosis

Study type

Interventional

Funder types

Other

Identifiers

NCT06361641
49RC23_0259
AO2721-44 (Other Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment

50 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Diagnostic

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

50 participants in 1 patient group

Phemop Cohort
Experimental group
Treatment:
Diagnostic Test: Monocytes signatures in myeloproliferative neoplasms at diagnosis

Trial contacts and locations

3

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Central trial contact

Anne-Catherine AUBE-NATHIER, PhD; Agathe GOUBAND, PharmD

Data sourced from clinicaltrials.gov

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