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High PD-L1 Expression Predicts for Worse Outcome of Leukemia Patients with Concomitant NPM1 and FLT3 Mutations

Compared to solid tumors, the role of PD-L1 in hematological malignancies is less explored, and the knowledge in this area is mostly limited to lymphomas. However, several studies indicated that PD-L1 is also overexpressed in myeloid malignancies. Successful treatment of the acute myeloid leukemia (...

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Autores principales: Brodská, Barbora, Otevřelová, Petra, Šálek, Cyril, Fuchs, Ota, Gašová, Zdenka, Kuželová, Kateřina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600137/
https://www.ncbi.nlm.nih.gov/pubmed/31185600
http://dx.doi.org/10.3390/ijms20112823
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author Brodská, Barbora
Otevřelová, Petra
Šálek, Cyril
Fuchs, Ota
Gašová, Zdenka
Kuželová, Kateřina
author_facet Brodská, Barbora
Otevřelová, Petra
Šálek, Cyril
Fuchs, Ota
Gašová, Zdenka
Kuželová, Kateřina
author_sort Brodská, Barbora
collection PubMed
description Compared to solid tumors, the role of PD-L1 in hematological malignancies is less explored, and the knowledge in this area is mostly limited to lymphomas. However, several studies indicated that PD-L1 is also overexpressed in myeloid malignancies. Successful treatment of the acute myeloid leukemia (AML) is likely associated with elimination of the residual disease by the immune system, and possible involvement of PD-L1 in this process remains to be elucidated. We analyzed PD-L1 expression on AML primary cells by flow cytometry and, in parallel, transcript levels were determined for the transcription variants v1 and v2. The ratio of v1/v2 cDNA correlated with the surface protein amount, and high v1/v2 levels were associated with worse overall survival (p = 0.0045). The prognostic impact of PD-L1 was limited to AML with mutated nucleophosmin and concomitant internal tandem duplications in the FLT3 gene (p less than 0.0001 for this particular AML subgroup).
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spelling pubmed-66001372019-07-16 High PD-L1 Expression Predicts for Worse Outcome of Leukemia Patients with Concomitant NPM1 and FLT3 Mutations Brodská, Barbora Otevřelová, Petra Šálek, Cyril Fuchs, Ota Gašová, Zdenka Kuželová, Kateřina Int J Mol Sci Article Compared to solid tumors, the role of PD-L1 in hematological malignancies is less explored, and the knowledge in this area is mostly limited to lymphomas. However, several studies indicated that PD-L1 is also overexpressed in myeloid malignancies. Successful treatment of the acute myeloid leukemia (AML) is likely associated with elimination of the residual disease by the immune system, and possible involvement of PD-L1 in this process remains to be elucidated. We analyzed PD-L1 expression on AML primary cells by flow cytometry and, in parallel, transcript levels were determined for the transcription variants v1 and v2. The ratio of v1/v2 cDNA correlated with the surface protein amount, and high v1/v2 levels were associated with worse overall survival (p = 0.0045). The prognostic impact of PD-L1 was limited to AML with mutated nucleophosmin and concomitant internal tandem duplications in the FLT3 gene (p less than 0.0001 for this particular AML subgroup). MDPI 2019-06-10 /pmc/articles/PMC6600137/ /pubmed/31185600 http://dx.doi.org/10.3390/ijms20112823 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brodská, Barbora
Otevřelová, Petra
Šálek, Cyril
Fuchs, Ota
Gašová, Zdenka
Kuželová, Kateřina
High PD-L1 Expression Predicts for Worse Outcome of Leukemia Patients with Concomitant NPM1 and FLT3 Mutations
title High PD-L1 Expression Predicts for Worse Outcome of Leukemia Patients with Concomitant NPM1 and FLT3 Mutations
title_full High PD-L1 Expression Predicts for Worse Outcome of Leukemia Patients with Concomitant NPM1 and FLT3 Mutations
title_fullStr High PD-L1 Expression Predicts for Worse Outcome of Leukemia Patients with Concomitant NPM1 and FLT3 Mutations
title_full_unstemmed High PD-L1 Expression Predicts for Worse Outcome of Leukemia Patients with Concomitant NPM1 and FLT3 Mutations
title_short High PD-L1 Expression Predicts for Worse Outcome of Leukemia Patients with Concomitant NPM1 and FLT3 Mutations
title_sort high pd-l1 expression predicts for worse outcome of leukemia patients with concomitant npm1 and flt3 mutations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600137/
https://www.ncbi.nlm.nih.gov/pubmed/31185600
http://dx.doi.org/10.3390/ijms20112823
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