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Early response evaluation by single cell signaling profiling in acute myeloid leukemia

Aberrant pro-survival signaling is a hallmark of cancer cells, but the response to chemotherapy is poorly understood. In this study, we investigate the initial signaling response to standard induction chemotherapy in a cohort of 32 acute myeloid leukemia (AML) patients, using 36-dimensional mass cyt...

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Autores principales: Tislevoll, Benedicte Sjo, Hellesøy, Monica, Fagerholt, Oda Helen Eck, Gullaksen, Stein-Erik, Srivastava, Aashish, Birkeland, Even, Kleftogiannis, Dimitrios, Ayuda-Durán, Pilar, Piechaczyk, Laure, Tadele, Dagim Shiferaw, Skavland, Jørn, Baliakas, Panagotis, Hovland, Randi, Andresen, Vibeke, Seternes, Ole Morten, Tvedt, Tor Henrik Anderson, Aghaeepour, Nima, Gavasso, Sonia, Porkka, Kimmo, Jonassen, Inge, Fløisand, Yngvar, Enserink, Jorrit, Blaser, Nello, Gjertsen, Bjørn Tore
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825407/
https://www.ncbi.nlm.nih.gov/pubmed/36611026
http://dx.doi.org/10.1038/s41467-022-35624-4
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author Tislevoll, Benedicte Sjo
Hellesøy, Monica
Fagerholt, Oda Helen Eck
Gullaksen, Stein-Erik
Srivastava, Aashish
Birkeland, Even
Kleftogiannis, Dimitrios
Ayuda-Durán, Pilar
Piechaczyk, Laure
Tadele, Dagim Shiferaw
Skavland, Jørn
Baliakas, Panagotis
Hovland, Randi
Andresen, Vibeke
Seternes, Ole Morten
Tvedt, Tor Henrik Anderson
Aghaeepour, Nima
Gavasso, Sonia
Porkka, Kimmo
Jonassen, Inge
Fløisand, Yngvar
Enserink, Jorrit
Blaser, Nello
Gjertsen, Bjørn Tore
author_facet Tislevoll, Benedicte Sjo
Hellesøy, Monica
Fagerholt, Oda Helen Eck
Gullaksen, Stein-Erik
Srivastava, Aashish
Birkeland, Even
Kleftogiannis, Dimitrios
Ayuda-Durán, Pilar
Piechaczyk, Laure
Tadele, Dagim Shiferaw
Skavland, Jørn
Baliakas, Panagotis
Hovland, Randi
Andresen, Vibeke
Seternes, Ole Morten
Tvedt, Tor Henrik Anderson
Aghaeepour, Nima
Gavasso, Sonia
Porkka, Kimmo
Jonassen, Inge
Fløisand, Yngvar
Enserink, Jorrit
Blaser, Nello
Gjertsen, Bjørn Tore
author_sort Tislevoll, Benedicte Sjo
collection PubMed
description Aberrant pro-survival signaling is a hallmark of cancer cells, but the response to chemotherapy is poorly understood. In this study, we investigate the initial signaling response to standard induction chemotherapy in a cohort of 32 acute myeloid leukemia (AML) patients, using 36-dimensional mass cytometry. Through supervised and unsupervised machine learning approaches, we find that reduction of extracellular-signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation in the myeloid cell compartment 24 h post-chemotherapy is a significant predictor of patient 5-year overall survival in this cohort. Validation by RNA sequencing shows induction of MAPK target gene expression in patients with high phospho-ERK1/2 24 h post-chemotherapy, while proteomics confirm an increase of the p38 prime target MAPK activated protein kinase 2 (MAPKAPK2). In this study, we demonstrate that mass cytometry can be a valuable tool for early response evaluation in AML and elucidate the potential of functional signaling analyses in precision oncology diagnostics.
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spelling pubmed-98254072023-01-09 Early response evaluation by single cell signaling profiling in acute myeloid leukemia Tislevoll, Benedicte Sjo Hellesøy, Monica Fagerholt, Oda Helen Eck Gullaksen, Stein-Erik Srivastava, Aashish Birkeland, Even Kleftogiannis, Dimitrios Ayuda-Durán, Pilar Piechaczyk, Laure Tadele, Dagim Shiferaw Skavland, Jørn Baliakas, Panagotis Hovland, Randi Andresen, Vibeke Seternes, Ole Morten Tvedt, Tor Henrik Anderson Aghaeepour, Nima Gavasso, Sonia Porkka, Kimmo Jonassen, Inge Fløisand, Yngvar Enserink, Jorrit Blaser, Nello Gjertsen, Bjørn Tore Nat Commun Article Aberrant pro-survival signaling is a hallmark of cancer cells, but the response to chemotherapy is poorly understood. In this study, we investigate the initial signaling response to standard induction chemotherapy in a cohort of 32 acute myeloid leukemia (AML) patients, using 36-dimensional mass cytometry. Through supervised and unsupervised machine learning approaches, we find that reduction of extracellular-signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation in the myeloid cell compartment 24 h post-chemotherapy is a significant predictor of patient 5-year overall survival in this cohort. Validation by RNA sequencing shows induction of MAPK target gene expression in patients with high phospho-ERK1/2 24 h post-chemotherapy, while proteomics confirm an increase of the p38 prime target MAPK activated protein kinase 2 (MAPKAPK2). In this study, we demonstrate that mass cytometry can be a valuable tool for early response evaluation in AML and elucidate the potential of functional signaling analyses in precision oncology diagnostics. Nature Publishing Group UK 2023-01-07 /pmc/articles/PMC9825407/ /pubmed/36611026 http://dx.doi.org/10.1038/s41467-022-35624-4 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Tislevoll, Benedicte Sjo
Hellesøy, Monica
Fagerholt, Oda Helen Eck
Gullaksen, Stein-Erik
Srivastava, Aashish
Birkeland, Even
Kleftogiannis, Dimitrios
Ayuda-Durán, Pilar
Piechaczyk, Laure
Tadele, Dagim Shiferaw
Skavland, Jørn
Baliakas, Panagotis
Hovland, Randi
Andresen, Vibeke
Seternes, Ole Morten
Tvedt, Tor Henrik Anderson
Aghaeepour, Nima
Gavasso, Sonia
Porkka, Kimmo
Jonassen, Inge
Fløisand, Yngvar
Enserink, Jorrit
Blaser, Nello
Gjertsen, Bjørn Tore
Early response evaluation by single cell signaling profiling in acute myeloid leukemia
title Early response evaluation by single cell signaling profiling in acute myeloid leukemia
title_full Early response evaluation by single cell signaling profiling in acute myeloid leukemia
title_fullStr Early response evaluation by single cell signaling profiling in acute myeloid leukemia
title_full_unstemmed Early response evaluation by single cell signaling profiling in acute myeloid leukemia
title_short Early response evaluation by single cell signaling profiling in acute myeloid leukemia
title_sort early response evaluation by single cell signaling profiling in acute myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825407/
https://www.ncbi.nlm.nih.gov/pubmed/36611026
http://dx.doi.org/10.1038/s41467-022-35624-4
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