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

Author

Listed:
  • 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
    University of Bergen)

  • Pilar Ayuda-Durán

    (The Norwegian Radium Hospital
    University of Oslo)

  • Laure Piechaczyk

    (The Norwegian Radium Hospital
    University of Oslo
    University of Oslo)

  • Dagim Shiferaw Tadele

    (Oslo University Hospital
    Department of Translational Hematology and Oncology Research)

  • 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
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Sonia Gavasso

    (University of Bergen
    University of Bergen)

  • Kimmo Porkka

    (Helsinki University Hospital Comprehensive Cancer Center)

  • Inge Jonassen

    (University of Bergen)

  • Yngvar Fløisand

    (University of Oslo
    Oslo University Hospital)

  • Jorrit Enserink

    (The Norwegian Radium Hospital
    University of Oslo
    University of Oslo)

  • Nello Blaser

    (University of Bergen)

  • Bjørn Tore Gjertsen

    (University of Bergen
    Haukeland University Hospital, Helse Bergen HF)

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.

Suggested Citation

  • Benedicte Sjo Tislevoll & Monica Hellesøy & Oda Helen Eck Fagerholt & Stein-Erik Gullaksen & Aashish Srivastava & Even Birkeland & Dimitrios Kleftogiannis & Pilar Ayuda-Durán & Laure Piechaczyk & Dagi, 2023. "Early response evaluation by single cell signaling profiling in acute myeloid leukemia," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35624-4
    DOI: 10.1038/s41467-022-35624-4
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    References listed on IDEAS

    as
    1. Friedman, Jerome H. & Hastie, Trevor & Tibshirani, Rob, 2010. "Regularization Paths for Generalized Linear Models via Coordinate Descent," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 33(i01).
    2. Simon, Noah & Friedman, Jerome H. & Hastie, Trevor & Tibshirani, Rob, 2011. "Regularization Paths for Cox's Proportional Hazards Model via Coordinate Descent," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 39(i05).
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