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

Benedicte Sjo Tislevoll, Monica Hellesøy, Oda Helen Eck Fagerholt, Stein-Erik Gullaksen, Aashish Srivastava, Even Birkeland, Dimitrios Kleftogiannis, Pilar Ayuda-Durán, Laure Piechaczyk, Dagim Shiferaw Tadele, Jørn Skavland, Panagotis Baliakas, Randi Hovland, Vibeke Andresen, Ole Morten Seternes, Tor Henrik Anderson Tvedt, Nima Aghaeepour, Sonia Gavasso, Kimmo Porkka, Inge Jonassen, Yngvar Fløisand, Jorrit Enserink, Nello Blaser () and Bjørn Tore Gjertsen ()
Additional contact information
Benedicte Sjo Tislevoll: University of Bergen
Monica Hellesøy: Haukeland University Hospital, Helse Bergen HF
Oda Helen Eck Fagerholt: University of Bergen
Stein-Erik Gullaksen: Haukeland University Hospital, Helse Bergen HF
Aashish Srivastava: K2 Haukeland University Hospital
Even Birkeland: The Proteomics Facility of the University of Bergen (PROBE), University of Bergen
Dimitrios Kleftogiannis: University of Bergen
Pilar Ayuda-Durán: The Norwegian Radium Hospital
Laure Piechaczyk: The Norwegian Radium Hospital
Dagim Shiferaw Tadele: Oslo University Hospital
Jørn Skavland: University of Bergen
Panagotis Baliakas: Uppsala University
Randi Hovland: Haukeland University Hospital
Vibeke Andresen: University of Bergen
Ole Morten Seternes: UiT-The Arctic University of Norway
Tor Henrik Anderson Tvedt: Oslo University Hospital
Nima Aghaeepour: Stanford University School of Medicine
Sonia Gavasso: University of Bergen
Kimmo Porkka: Helsinki University Hospital Comprehensive Cancer Center
Inge Jonassen: University of Bergen
Yngvar Fløisand: University of Oslo
Jorrit Enserink: The Norwegian Radium Hospital
Nello Blaser: University of Bergen
Bjørn Tore Gjertsen: University of Bergen

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-022-35624-4

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