# Prognostic utility of macrophage polarization (CD68/CD163 ratio) in Egyptian JAK2 positive myeloproliferative neoplasm patients: a single center study

## TL;DR

This study shows that the CD68/CD163 macrophage ratio can predict complications and outcomes in patients with a specific type of blood cancer.

## Contribution

The study identifies the CD68/CD163 macrophage ratio as a novel prognostic marker in JAK2-positive myeloproliferative neoplasm patients.

## Key findings

- A CD68/CD163 ratio >1.63 is linked to shorter thrombosis-free and fibrosis-free survival in MPN patients.
- The ratio predicts thrombosis (AUC=0.677) and secondary myelofibrosis (AUC=0.779) with high accuracy.
- CD68 alone shows excellent diagnostic accuracy for predicting secondary myelofibrosis (AUC=0.851).

## Abstract

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.

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.

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%).

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.

The online version contains supplementary material available at 10.1186/s13000-025-01727-x.