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

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.

Automated summary

Although PD-L1 overexpression is observed in solid tumors, its expression patterns in acute myeloid leukemia (AML) are not well studied. This study shows that PD-L1 expression is significantly upregulated in AML cases with activating mutations in JAK2/STATs compared to wildtype controls. There is a positive correlation between phosphorylated STAT3 expression and PD-L1 expression. The CPS scoring system could be used to quantitatively measure PD-L1 expression in leukemias and JAK2/STATs mutant AML could be potential candidates for checkpoint inhibitor trials.