Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia
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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.
In: Cancers, Vol. 12, No. 3, 709, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia
AU - Aasebø, Elise
AU - Berven, Frode S
AU - Bartaula-Brevik, Sushma
AU - Stokowy, Tomasz
AU - Hovland, Randi
AU - Vaudel, Marc
AU - Døskeland, Stein Ove
AU - McCormack, Emmet
AU - Batth, Tanveer S
AU - Olsen, Jesper V
AU - Bruserud, Øystein
AU - Selheim, Frode
AU - Hernandez-Valladares, Maria
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.3390/cancers12030709
DO - 10.3390/cancers12030709
M3 - Journal article
C2 - 32192169
VL - 12
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 3
M1 - 709
ER -
ID: 239208728