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Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a hematological cancer that mainly affects the elderly. Although complete remission (CR) is achieved for the majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Understanding biological factors that...

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Autores principales: Aasebø, Elise, Berven, Frode S., Bartaula-Brevik, Sushma, Stokowy, Tomasz, Hovland, Randi, Vaudel, Marc, Døskeland, Stein Ove, McCormack, Emmet, Batth, Tanveer S., Olsen, Jesper V., Bruserud, Øystein, Selheim, Frode, Hernandez-Valladares, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140113/
https://www.ncbi.nlm.nih.gov/pubmed/32192169
http://dx.doi.org/10.3390/cancers12030709
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author Aasebø, Elise
Berven, Frode S.
Bartaula-Brevik, Sushma
Stokowy, Tomasz
Hovland, Randi
Vaudel, Marc
Døskeland, Stein Ove
McCormack, Emmet
Batth, Tanveer S.
Olsen, Jesper V.
Bruserud, Øystein
Selheim, Frode
Hernandez-Valladares, Maria
author_facet Aasebø, Elise
Berven, Frode S.
Bartaula-Brevik, Sushma
Stokowy, Tomasz
Hovland, Randi
Vaudel, Marc
Døskeland, Stein Ove
McCormack, Emmet
Batth, Tanveer S.
Olsen, Jesper V.
Bruserud, Øystein
Selheim, Frode
Hernandez-Valladares, Maria
author_sort Aasebø, Elise
collection PubMed
description Acute myeloid leukemia (AML) is a hematological cancer that mainly affects the elderly. Although complete remission (CR) is achieved for the majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Understanding biological factors that determine relapse has become of major clinical interest in AML. We utilized liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify the protein changes and protein phosphorylation events associated with AML relapse in primary cells from 41 AML patients at time of diagnosis. Patients were defined as relapse-free if they had not relapsed within a five-year clinical follow-up after AML diagnosis. Relapse was associated with increased expression of RNA processing proteins and decreased expression of V-ATPase proteins. We also observed an increase in phosphorylation events catalyzed by cyclin-dependent kinases (CDKs) and casein kinase 2 (CSK2). The biological relevance of the proteome findings was supported by cell proliferation assays using inhibitors of V-ATPase (bafilomycin), CSK2 (CX-4945), CDK4/6 (abemaciclib) and CDK2/7/9 (SNS-032). While bafilomycin preferentially inhibited the cells from relapse patients, the kinase inhibitors were less efficient in these cells. This suggests that therapy against the upregulated kinases could also target the factors inducing their upregulation rather than their activity. This study, therefore, presents markers that could help predict AML relapse and direct therapeutic strategies.
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spelling pubmed-71401132020-04-13 Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia Aasebø, Elise Berven, Frode S. Bartaula-Brevik, Sushma Stokowy, Tomasz Hovland, Randi Vaudel, Marc Døskeland, Stein Ove McCormack, Emmet Batth, Tanveer S. Olsen, Jesper V. Bruserud, Øystein Selheim, Frode Hernandez-Valladares, Maria Cancers (Basel) Article Acute myeloid leukemia (AML) is a hematological cancer that mainly affects the elderly. Although complete remission (CR) is achieved for the majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Understanding biological factors that determine relapse has become of major clinical interest in AML. We utilized liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify the protein changes and protein phosphorylation events associated with AML relapse in primary cells from 41 AML patients at time of diagnosis. Patients were defined as relapse-free if they had not relapsed within a five-year clinical follow-up after AML diagnosis. Relapse was associated with increased expression of RNA processing proteins and decreased expression of V-ATPase proteins. We also observed an increase in phosphorylation events catalyzed by cyclin-dependent kinases (CDKs) and casein kinase 2 (CSK2). The biological relevance of the proteome findings was supported by cell proliferation assays using inhibitors of V-ATPase (bafilomycin), CSK2 (CX-4945), CDK4/6 (abemaciclib) and CDK2/7/9 (SNS-032). While bafilomycin preferentially inhibited the cells from relapse patients, the kinase inhibitors were less efficient in these cells. This suggests that therapy against the upregulated kinases could also target the factors inducing their upregulation rather than their activity. This study, therefore, presents markers that could help predict AML relapse and direct therapeutic strategies. MDPI 2020-03-17 /pmc/articles/PMC7140113/ /pubmed/32192169 http://dx.doi.org/10.3390/cancers12030709 Text en © 2020 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
Aasebø, Elise
Berven, Frode S.
Bartaula-Brevik, Sushma
Stokowy, Tomasz
Hovland, Randi
Vaudel, Marc
Døskeland, Stein Ove
McCormack, Emmet
Batth, Tanveer S.
Olsen, Jesper V.
Bruserud, Øystein
Selheim, Frode
Hernandez-Valladares, Maria
Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia
title Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia
title_full Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia
title_fullStr Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia
title_full_unstemmed Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia
title_short Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia
title_sort proteome and phosphoproteome changes associated with prognosis in acute myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140113/
https://www.ncbi.nlm.nih.gov/pubmed/32192169
http://dx.doi.org/10.3390/cancers12030709
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