Acute myeloid leukemias with JAK2/STAT mutations are associated with PD-L1 upregulation

Abstract

Even though overexpression of the immune checkpoint protein, programmed cell death ligand-1 (PD-L1), is observed in solid tumors, its expression patterns in acute myeloid leukemia remain understudied. As activation of the JAK/STAT pathway has been shown to enhance PD-L1 expression in preclinical models, we evaluated biopsies from AML patients with activating mutations in JAK2/STATs. PD-L1 expression was significantly upregulated in JAK2/STAT mutant cases when compared to JAK2 wildtype controls as demonstrated by PD-L1 immunohistochemistry staining and quantified using the combined positive score (CPS) system. There is significant overexpression of phosphorylated STAT3 expression in patients with oncogenic JAK2 activation and a positive correlation between p-STAT3 and PD-L1 expression. In conclusion, we demonstrate the CPS scoring system could be applied as a quantitative measure of PD-L1 expression in leukemias and that JAK2/STATs mutant AML can be potential candidates for checkpoint inhibitor trials.

Keywords:

• Acute myeloid leukemia (AML)
• programmed cell death ligand-1 (PD-L1)
• JAK2 / STAT mutation
• combined positive score (CPS)

Acknowledgments

The authors thank the technical support from the histology, immunohistochemistry, and flow cytometry laboratories in the Department of Pathology at Montefiore Medical Center, Albert Einstein College of Medicine.

Author contributions

X.T. conceived and designed the study; A.V. and Y.W. designed the study and edited the final manuscript; J.N.C., and J.C. collected data; Q.W., Y.F., Y.S., Y.W., and X.T. evaluated histology, immunostaining, and case diagnoses; N.S., R.A.S., N.K., M.K., I.M., A.S., K.G., A.V., M.G., and S.G. provided patient care, clinical information and case discussions; J.N.C. conducted statistical analysis; J.N.C. and X.T. drafted the manuscript; all authors reviewed the manuscript for important intellectual content; all authors approved the manuscript before submission.

Ethics Approval

This study was approved by the Montefiore Medical Center Institutional Review Board (2021-13556).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.