Relevance of Peripheral Cells in the Pathophysiology of Chronic Myelomonocytic Leukemia (CMML)

NCT03280888 | Recruiting

• 1 other identifier: 13-PP-11
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic Myelomonocytic Leukemia (CMML) is the most frequent of myelodysplastic/myeloproliferative syndromes, as defined by the WHO classification of myeloid malignancies. The median age at diagnosis is around 70 years with a strong male predominance. CMML is a clonal disease of the bone marrow hematopoietic stem cell mainly characterized by persistent monocytosis (\>1x109/L) and the presence of immature dysplastic granulocytes in the peripheral blood of CMML patients. Allogeneic stem cell transplantation (ASCT) remains the only curative option in CMML. However, CMML patients are rarely eligible for this kind of therapy, mainly due to their advanced age. The gold standard treatment of CMML thus remains hydroxyurea, which is usually initiated when the disease becomes proliferative, and demethylating agents, which could be efficient in the most aggressive forms of CMML. Nevertheless, the pathogenesis of CMML remains poorly understood and new therapies are urgently needed for patients in treatment failure. In recent years, a large numbers of gene mutations have been discovered in CMML, none of which are specific of this entity, as they can be encountered with different frequencies in other myeloid neoplasms. These mutated genes encode signaling molecules (NRAS, KRAS, CBL, JAK2, FLT3 and several members of the Notch pathway), epigenetic regulators (TET2, ASXL1, EZH2, IDH1, IDH2,.) and splicing factors (SF3B1, SRSF2, ZRSF2). Mutations in the transcription regulators RUNX1, NPM1 and TP53 have also been reported in CMML. However, the role of these mutations in leukemogenesis is still unclear. CMML is also characterized by defects in monocyte to macrophage differentiation. These defects in monocyte differentiation can be attributed to the presence of immature dysplastic granulocytes that secrete high levels of alpha-defensins HNP1-3 that antagonize the purinergic receptor P2RY6 in CMML patients. These CD14-/CD15+/CD24+ immature granulocytes that belong to the same clone than the leukemic monocytes seem to have immunosuppressive properties ressembling those of the myeloid-derived suppressor cells (MDCS) described in solid tumours. Whether these immature granulocytes contribute to autoimmune manifestations or immunoescape and progression of CMML is a conendrum and remains to be determined. In this context, the proposed project aims at identifying news insights into the pathophysiology of CMML through a better definition of the phenotype and function of monocytes and immature granulocytes that characterize this pathology.

Conditions

Chronic Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Characterization of molecular mechanisms

  Characterization of the molecular mechanisms involved in the lack of differentiation of monocytes originating from patients with CML.

  at 3 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

patients with chronic myelomonocytic leukemia

You may qualify if:

• Patients newly diagnosed or undergoing treatment in the Clinical Hematology department of the participating establishments

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (1)

CHU de Nice

Nice, 06000, France

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Laurence Legros, PH

CONTACT

+33 (0)4 92 03 58 41; legros.l@chu-nice.fr

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2017
• First Posted: September 13, 2017
• Study Start: November 5, 2014
• Primary Completion (Estimated): November 5, 2027
• Study Completion (Estimated): November 5, 2028
• Last Updated: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)