Chronic myelomonocytic leukemia revisited: A comprehensive review with emphasis on the oligomonocytic subtype

Oligomonocytic chronic myelomonocytic leukemia (OM-CMML) is defined by an absolute monocyte count of 0.5-<1.0 × 10⁹/L with relative monocytosis ≥10%. This entity was formally recognized in the 2022 WHO Classification of Haematolymphoid Tumours and the International Consensus Classification, representing a paradigm shift from prior thresholds requiring monocyte counts ≥1.0 × 10⁹/L. This change in criteria captures a clinically and biologically meaningful disease state with independent prognostic significance and an almost 50% five-year cumulative incidence of progression to overt CMML. However, this change has also expanded the diagnostic boundaries of OM-CMML into territory previously classified as myelodysplastic syndromes (MDS). Accurate diagnosis requires integration of bone marrow morphology, flow cytometric monocyte subset partitioning, and genomic profiling. Cases harboring biallelic TET2 inactivation or TET2+SRSF2 co-mutation show the highest bone marrow monocyte burden, frequent classical monocyte (MO1; CD14+/CD16-) elevation, and highest progression risk representing biologically true OM-CMML, whereas SF3B1-mutated and biallelic TP53 mutated cases show MDS-directed biology and warrant reclassification. This review synthesizes current diagnostic frameworks, molecular heterogeneity, risk stratification approaches, and evolving classification proposals, thereby providing a practical guide for pathologists navigating OM-CMML in the modern genomic era.