Programmed Death-Ligand 1 (PD-L1) Expression in Patients with Primary or Secondary Myelofibrosis

It has been described in mice models that Primary Myelofibrosis (PMF) 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. To prove this hypothesis, we quantified PD-L1 expression on 29 bone marrow (BM) biopsies. We created a scoring system to quantify PD-L1 expression in megakaryocytes. 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 to the control group with a score of 212.6 vs 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 to the control group with score of 205.9 vs 121.1(t-value 2.12,p-value 0.021). There was no difference in the PD-L1 score between the JAK2 negative vs the control group 187.2 vs 121.1 (t-value 1.02,p-value 0.162). These findings suggest that PMF patients with a JAK2 mutation have a higher PD-L1 expression in megakaryocytes compared to 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.