Introduction
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN)
characterized by constitutional activation of the JAK-STAT signaling
pathway and bone marrow (BM) fibrosis which leads to decreased
peripheral blood counts, pro-inflammatory state, and a potential for
transformation to acute myeloid leukemia (AML). The median age at
presentation is 65 years [2,3]. JAK2-V617F is the most common
mutation in PMF and is found in 50-60% of patients [4]. The only
curative treatment option currently available is allogeneic stem cell
transplant. However, most patients are ineligible because of advanced
age and comorbidities [5]. Ruxolitinib and fedratinib, JAK2
inhibitors, are the only FDA approved treatment for intermediate/high
risk PMF patients [6,7]. However, those drugs have their limitations
and only improve symptoms and decrease splenomegaly, without an overall
survival benefit [6,7]. Therefore, there is a significant unmet need
for treatment options in this patient population.
Prestipino et al. discovered that mice models with JAK2-V617F mutated
MPN generally have an increased expression of PD-L1 that leads to cancer
immune evasion by inhibiting the antitumor effect of the T lymphocytes
against cancer cells [1]. Checkpoint inhibitors are monoclonal
antibodies that block the interaction between PD-L1 and its receptor,
allowing the immune system to fight cancer cells with an enhanced
antitumor response. Pembrolizumab was the first checkpoint inhibitor
approved by the FDA for patients with metastatic non-small-cell lung
cancer with >50% PD-L1 expression in tumor cells by
immunohistochemistry stain. In this subset of patients, pembrolizumab
was more effective than systemic chemotherapy [9].
In this paper, we compared the PD-L1 expression among patients with
JAK2-mutated PMF versus JAK2-unmutated PMF patients versus normal
controls without no PMF or JAK2 mutation.