CML-985: Involvement of CD206+ Macrophages in Altered Metabolic Profile of CD34+ CML Cells via Secretory Cytokines

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder arising from pluripotent hematopoietic stem cells marked by abnormal blood cell production, the BCR-ABL1 fusion gene, and dysregulated immune responses. Although oral tyrosine kinase inhibitors have perceptibly improved disease prognosis, therapeutic challenges remain, particularly in achieving sustained treatment-free remission. Recent advances in immunotherapy offer promising avenues to further enhance disease control and long-term patient outcomes. This study investigates the alterations in innate immune regulations, emphasizing especially M2 macrophage population and their functional implication in CML. Whole blood isolated from CML patients and healthy volunteers was analyzed using flow cytometry with CD45 + /CD14 + /CD11b + /CD163 + /CD206 + panel and expressed a significantly higher proportion of CD163 + /CD206 + M2 macrophages in CML samples compared to healthy controls ( P < 0.01). Subsequently, CD11b + cells were isolated from peripheral blood mononuclear cells and polarized with phorbol myristate acetate, followed by IL-4, IL-13, and serum from CML or healthy donors. Confocal microscopy revealed increased expression of CD206 in CML-derived macrophages ( P < 0.01). Metabolic profiling of CD34 + CML cells cocultured with conditioned supernatant indicated elevated NAD + and ATP levels in CML samples, suggesting enhanced oxidative metabolism. Cytokine array of macrophage-conditioned media identified significantly higher levels of IL-1ra, IL-6, IL-8, CXCL10, CCL1 (MCP-1), and MIF in CML patients. These findings align with previous reports indicating increased macrophage expression in CML and myelodysplastic syndromes. Collectively, our data demonstrate an expansion of immunosuppressive M2 macrophages in CML, characterized by elevated CD206 + expression and altered metabolic profiles, which may contribute to disease progression and immune evasion.