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NPM1 and DNMT3A mutations are associated with distinct blast immunophenotype in acute myeloid leukemia
K. Kuželová, B. Brodská, J. Marková, M. Petráčková, J. Schetelig, Š. Ransdorfová, Z. Gašová, C. Šálek
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed Central od 2012
Europe PubMed Central od 2012 do Před 1 rokem
Taylor & Francis Open Access od 2020-01-01
ROAD: Directory of Open Access Scholarly Resources od 2012
Odkazy
PubMed
35558161
DOI
10.1080/2162402x.2022.2073050
Knihovny.cz E-zdroje
- MeSH
- akutní myeloidní leukemie * diagnóza genetika MeSH
- antigeny CD274 genetika MeSH
- biologické markery MeSH
- buněčný receptor 2 viru hepatitidy A genetika MeSH
- DNA methyltransferasa 3A * genetika MeSH
- lidé MeSH
- mutace MeSH
- nukleofosmin * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The immune system is important for elimination of residual leukemic cells during acute myeloid leukemia (AML) therapy. Anti-leukemia immune response can be inhibited by various mechanisms leading to immune evasion and disease relapse. Selected markers of immune escape were analyzed on AML cells from leukapheresis at diagnosis (N = 53). Hierarchical clustering of AML immunophenotypes yielded distinct genetic clusters. In the absence of DNMT3A mutation, NPM1 mutation was associated with decreased HLA expression and low levels of other markers (CLIP, PD-L1, TIM-3). Analysis of an independent cohort confirmed decreased levels of HLA transcripts in patients with NPM1 mutation. Samples with combined NPM1 and DNMT3A mutations had high CLIP surface amount suggesting reduced antigen presentation. TIM-3 transcript correlated not only with TIM-3 surface protein but also with CLIP and PD-L1. In our cohort, high levels of TIM-3/PD-L1/CLIP were associated with lower survival. Our results suggest that AML genotype is related to blast immunophenotype, and that high TIM-3 transcript levels in AML blasts could be a marker of immune escape. Cellular pathways regulating resistance to the immune system might contribute to the predicted response to standard therapy of patients in specific AML subgroups and should be targeted to improve AML treatment.
Clinical Department Institute of Hematology and Blood Transfusion Prague Czech Republic
Department of Apheresis Institute of Hematology and Blood Transfusion Prague Czech Republic
Department of Cytogenetics Institute of Hematology and Blood Transfusion Prague Czech Republic
Department of Proteomics Institute of Hematology and Blood Transfusion Prague Czech Republic
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- $a The immune system is important for elimination of residual leukemic cells during acute myeloid leukemia (AML) therapy. Anti-leukemia immune response can be inhibited by various mechanisms leading to immune evasion and disease relapse. Selected markers of immune escape were analyzed on AML cells from leukapheresis at diagnosis (N = 53). Hierarchical clustering of AML immunophenotypes yielded distinct genetic clusters. In the absence of DNMT3A mutation, NPM1 mutation was associated with decreased HLA expression and low levels of other markers (CLIP, PD-L1, TIM-3). Analysis of an independent cohort confirmed decreased levels of HLA transcripts in patients with NPM1 mutation. Samples with combined NPM1 and DNMT3A mutations had high CLIP surface amount suggesting reduced antigen presentation. TIM-3 transcript correlated not only with TIM-3 surface protein but also with CLIP and PD-L1. In our cohort, high levels of TIM-3/PD-L1/CLIP were associated with lower survival. Our results suggest that AML genotype is related to blast immunophenotype, and that high TIM-3 transcript levels in AML blasts could be a marker of immune escape. Cellular pathways regulating resistance to the immune system might contribute to the predicted response to standard therapy of patients in specific AML subgroups and should be targeted to improve AML treatment.
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