PD‐L1 expression in megakaryocytes and its clinicopathological features in primary myelofibrosis patients

Abstract

Abstract Myeloproliferative neoplasms (MPNs) are characterized by upregulation of proinflammatory cytokines and immune dysregulation, which provide a reasonable basis for immunotherapy in patients. Megakaryocytes are crucial in the pathogenesis of primary myelofibrosis (PMF), the most clinically aggressive subtype of MPN. In this study, we aimed to explore PD‐L1 (programmed death‐ligand 1) expression in megakaryocytes and its clinical implications in PMF. We analyzed PD‐L1 expression on megakaryocytes in PMF patients by immunohistochemistry and correlated the results with clinicopathological features and molecular aberrations. We employed a two‐tier grading system considering both the proportion of cells positively stained and the intensity of staining. Among the 85 PMF patients, 41 (48%) showed positive PD‐L1 expression on megakaryocytes with the immune‐reactive score ranging from 1 to 12. PD‐L1 expression correlated closely with higher white blood cell count (p = 0.045), overt myelofibrosis (p = 0.010), JAK2V617F mutation (p = 0.011), and high‐molecular risk mutations (p = 0.045), leading to less favorable overall survival in these patients (hazard ratio 0.341, 95% CI 0.135–0.863, p = 0.023). Our study provides unique insights into the interaction between immunologic and molecular phenotypes in PMF patients. Future work to explore the translational potential of PD‐L1 in the clinical setting is needed.

Keywords

• PD‐L1
• primary myelofibrosis
• megakaryocyte
• JAK2
• checkpoint
• SP142