MAC-AGE is a single-center study designed to characterize bone marrow macrophages in patients with chronic myelomonocytic leukemia (CMML) and to compare them with macrophages from age-matched controls undergoing elective total hip arthroplasty. Phenotypic, transcriptional and functional analyses will be performed using spectral/multiparametric flow cytometry, single-cell RNA sequencing and ex vivo functional assays. The study aims to identify CMML-associated macrophage alterations and potential therapeutic targets within the bone marrow immune microenvironment.
Group Patients with CML
Age ≥ 55 years
Confirmed diagnosis of chronic myelomonocytic leukaemia (CML) according to WHO criteria (2022 edition)
Patient registered with or covered by a social security scheme
Group 1
Active infection or acute inflammatory condition
Treatment with chemotherapy or immunosuppressants within the 4 weeks prior to the procedure
Medical contraindication to bone marrow aspiration
Parallel
Bone marrow and blood samples
Procedure/Surgery2 mL of additional bone marrow are collected during a planned standard-of-care sternal or iliac aspiration, together with 40 mL of additional peripheral blood during routine blood sampling.
Bone marrow sample
Procedure/Surgery2 mL of additional bone marrow are collected during a planned standard-of-care sternal or iliac aspiration, together with 40 mL of additional peripheral blood during routine blood sampling.
Phenotypic and transcriptional differences in bone marrow macrophages between CMML patients and age-matched controls
Bone marrow macrophages will be characterized by spectral/multiparametric flow cytometry, including CD80, CD86, HLA-DR, CD163, CD206, CD209, CD200R, SIRPα and MARCO, and by targeted RT-qPCR and/or exploratory single-cell RNA sequencing. Differential macrophage populations and gene-expression programs will be compared between the two groups.
Functional and immunomodulatory profile of bone marrow macrophages
Ex vivo cytokine secretion (including TNF-α, IL-10, CCL2 and TGF-β), phagocytosis of apoptotic or leukemic targets, modulation of naïve CD4+ T-cell polarization (Th1 versus Th2), and response to experimental pharmacological modulators targeting non-canonical caspase-8 and cathepsin B will be assessed and compared between groups
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Centre Hospitalier Universitaire de Nice
Lead sponsor
INSERM U1065 - Centre Méditerranéen de Médecine Moléculaire (C3M)
Collaborator
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