Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia.
V-ATPase
acute myeloid leukemia
kinase
markers
mass spectrometry
patient relapse
phosphoproteome
proteome
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
17 Mar 2020
17 Mar 2020
Historique:
received:
04
02
2020
revised:
05
03
2020
accepted:
13
03
2020
entrez:
21
3
2020
pubmed:
21
3
2020
medline:
21
3
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32192169
pii: cancers12030709
doi: 10.3390/cancers12030709
pmc: PMC7140113
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Kreftforeningen
ID : 100933
Organisme : Novo Nordisk
ID : NNF14CC0001
Organisme : Norges Forskningsråd
ID : 245979/F50
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