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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:64 |
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| Enthalten in: |
Leukemia & lymphoma - 64(2023), 10 vom: 30. Okt., Seite 1662-1672 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chai, Jiani [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.02.2024 Date Revised 01.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/10428194.2023.2232494 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359253792 |
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| 245 | 1 | 0 | |a Acute myeloid leukemias with JAK2/STAT mutations are associated with PD-L1 upregulation |
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| 500 | |a Date Revised 01.03.2024 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute myeloid leukemia (AML) | |
| 650 | 4 | |a JAK2 / STAT mutation | |
| 650 | 4 | |a combined positive score (CPS) | |
| 650 | 4 | |a programmed cell death ligand-1 (PD-L1) | |
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| 650 | 7 | |a JAK2 protein, human |2 NLM | |
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| 650 | 7 | |a Janus Kinase 2 |2 NLM | |
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| 650 | 7 | |a STAT Transcription Factors |2 NLM | |
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| 700 | 1 | |a Choudhuri, Jui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Yanan |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Kamel, Josette |e verfasserin |4 aut | |
| 700 | 1 | |a Shah, Nishi |e verfasserin |4 aut | |
| 700 | 1 | |a Sica, R Alejandro |e verfasserin |4 aut | |
| 700 | 1 | |a Kornblum, Noah |e verfasserin |4 aut | |
| 700 | 1 | |a Konopleva, Marina |e verfasserin |4 aut | |
| 700 | 1 | |a Mantzaris, Ioannis |e verfasserin |4 aut | |
| 700 | 1 | |a Shastri, Aditi |e verfasserin |4 aut | |
| 700 | 1 | |a Gritsman, Kira |e verfasserin |4 aut | |
| 700 | 1 | |a Verma, Amit |e verfasserin |4 aut | |
| 700 | 1 | |a Goldfinger, Mendel |e verfasserin |4 aut | |
| 700 | 1 | |a Goel, Swati |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yanhua |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Xuejun |e verfasserin |4 aut | |
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