Abstract
BACKGROUND: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders with variable clinical outcomes influenced by the bone marrow microenvironment. Tumor-associated macrophages (TAMs), particularly the M1 (CD68⁺) and M2 (CD163⁺) subtypes, play critical roles in inflammation, fibrosis, and immune modulation. This study evaluates CD68- and CD163-positive macrophage frequencies across MPN subtypes and their clinical/prognostic significance. METHODS: In this retrospective cohort study, 121 patients with histopathologically confirmed BCR::ABL1-negative, JAK2V617F-positive MPNs were assessed for CD68 and CD163 expression. The CD68/CD163 ratio was analyzed for associations with thrombosis, leukemic/fibrotic transformation, and survival outcomes using receiver operating characteristic (ROC) curves and Kaplan-Meier analyses. RESULTS: A CD68/CD163 ratio > 1.63 correlated with shorter thrombosis-free survival (41.4 vs. 68.2 months; p = 0.001; hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.45-4.14) and secondary myelofibrosis progression-free survival (48.3 vs. 79.0 months; p = 0.001; HR 2.67, 95% CI 1.55-4.60). The ratio predicted thrombosis (area under the curve [AUC] = 0.677, 95% CI 0.58-0.77; p = 0.001) and secondary myelofibrosis (AUC = 0.779, 95% CI 0.69-0.87; p < 0.001). CD68 alone showed excellent diagnostic accuracy for the prediction of secondary myelofibrosis (AUC = 0.851, 95% CI 0.78-0.92; specificity = 100%). CONCLUSIONS: TAM polarization, reflected by the CD68/CD163 ratio, is a prognostic marker in MPNs, particularly for thrombosis and fibrotic progression. These findings support integrating TAM profiling into routine histopathology and suggest macrophage-targeted therapies as potential strategies for MPN management.