Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Chronic myelomonocytic leukemia without increased classical monocyte subsets exhibits a distinct genetic profile, including frequent CBL mutations.

Abstract

OBJECTIVES: To characterize the genetic profiles of chronic myelomonocytic leukemia (CMML) cases that do not exhibit increased classical monocyte (CM) subsets in -peripheral blood. METHODS: A total of 174 patients with CMML who were treatment-naive for hypomethylating agents and had undergone next-generation sequencing (NGS) testing were analyzed. Among these, 152 patients (87.4%) demonstrated increased CM subsets (>94%) by flow cytometry (CM group), while 22 patients (12.6%) did not show increased CM subsets (<=94%) (non-CM group). RESULTS: Patients in the CM and non-CM groups exhibited comparable demographic characteristics, complete blood count parameters, CMML subtype (myelodysplastic vs myeloproliferative), and disease grade (CMML-1 vs CMML-2). The NGS analysis revealed significant enrichment of CBL (45.5% vs 11.2%, P < .001), IDH2 (18.2% vs 4.6%, P = .035), RAS pathway gene mutations (59.1% vs 34.2%, P = .033), and a lower frequency of TET2 mutations (40.9% vs 67.1%, P = .031) in the non-CM group compared with the CM group. Patients with CMML in the non-CM group also exhibited fewer cytogenetic abnormalities compared with those in the CM group (0% vs 22.5%, P = .039). Both non-CM and CBL-mutated CMML showed higher expression of HLA-DR by flow cytometry. No statistically significant differences were observed between the 2 groups in overall survival or acute myeloid leukemia-free survival. CONCLUSIONS: Chronic myelomonocytic leukemia without increased CM subsets is associated with a distinct genetic profile characterized by enrichment of CBL mutations. Mechanistically, we hypothesize that CBL mutations promote proinflammatory signaling that contributes to normalization of CM partitioning.