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

Autor: Chai J; Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Choudhuri J; Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Wang Q; Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Fang Y; Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Shi Y; Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Kamel J; Department of Hematology-Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Shah N; Department of Hematology-Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Sica RA; Department of Hematology-Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Kornblum N; Department of Hematology-Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Konopleva M; Department of Hematology-Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Mantzaris I; Department of Hematology-Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Shastri A; Department of Hematology-Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Gritsman K; Department of Hematology-Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Verma A; Department of Hematology-Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Goldfinger M; Department of Hematology-Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Goel S; Department of Hematology-Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Wang Y; Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Tian X; Department of Pathology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA.; Department of Pathology, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
Jazyk: angličtina
Zdroj: Leukemia & lymphoma [Leuk Lymphoma] 2023 Oct; Vol. 64 (10), pp. 1662-1672. Date of Electronic Publication: 2023 Jul 10.
DOI: 10.1080/10428194.2023.2232494
Abstrakt: 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.
Databáze: MEDLINE
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