Programmed death‐ligand 1 expression in patients with primary or secondary myelofibrosis

Abstract

Abstract Background It has been described in mice models that myeloproliferative neoplasm (MPN) with JAK2‐V617F mutation has an increased expression of programmed death‐ligand 1 (PD‐L1) in megakaryocytes leading to cancer immune evasion by inhibiting the T‐lymphocytes. Aims To quantify and compare the PD‐L1 expression on bone marrow (BM) of patients with MPN JAK2 positive, negative, and normal controls. Methods We collected BM of patients with MPN JAK2 positive, negative and normal controls from 1990 to 2019. We also created a scoring system to quantify PD‐L1 expression in megakaryocytes. Results We obtained 14 BM with JAK2 positive PMF, 5 JAK2 negative PMF, and 10 patients with normal BM biopsies. PD‐L1 expression was higher in the JAK2 positive group compared with the control group with a score of 212.6 versus 121.1 (t‐value 2.05, p‐value 0.025). In addition, the score was higher in the PMF group regardless of JAK2 mutational status when compared with the control group with score of 205.9 versus 121.1 (t‐value 2.12, p‐value 0.021). There was no difference in the PD‐L1 score between the JAK2 negative versus the control group 187.2 versus 121.1 (t‐value 1.02, p‐value 0.162). Conclusion These findings suggest that PMF patients with a JAK2 mutation have a higher PD‐L1 expression in megakaryocytes compared with the control group. We postulate that the combination of checkpoint and JAK2 inhibitors may be an active treatment option in JAK2 mutated PMF given the higher PD‐L1 expression.

Keywords

• immunotherapy
• JAK/STAT pathway
• PD‐L1
• primary myelofibrosis
• secondary myelofibrosis