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Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib

SE. Gullaksen, J. Skavland, S. Gavasso, V. Tosevski, K. Warzocha, C. Dumrese, A. Ferrant, T. Gedde-Dahl, A. Hellmann, J. Janssen, B. Labar, A. Lang, W. Majeed, G. Mihaylov, J. Stentoft, L. Stenke, J. Thaler, N. Thielen, G. Verhoef, J. Voglova, G....

. 2017 ; 102 (8) : 1361-1367. [pub] 20170518

Language English Country Italy

Document type Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc18025011

Monitoring of single cell signal transduction in leukemic cellular subsets has been proposed to provide deeper understanding of disease biology and prognosis, but has so far not been tested in a clinical trial of targeted therapy. We developed a complete mass cytometry analysis pipeline for characterization of intracellular signal transduction patterns in the major leukocyte subsets of chronic phase chronic myeloid leukemia. Changes in phosphorylated Bcr-Abl1 and the signaling pathways involved were readily identifiable in peripheral blood single cells already within three hours of the patient receiving oral nilotinib. The signal transduction profiles of healthy donors were clearly distinct from those of the patients at diagnosis. Furthermore, using principal component analysis, we could show that phosphorylated transcription factors STAT3 (Y705) and CREB (S133) within seven days reflected BCR-ABL1IS at three and six months. Analyses of peripheral blood cells longitudinally collected from patients in the ENEST1st clinical trial showed that single cell mass cytometry appears to be highly suitable for future investigations addressing tyrosine kinase inhibitor dosing and effect. (clinicaltrials.gov identifier: 01061177).

Centre of Cancer Biomarkers CCBIO Department of Clinical Science Precision Oncology Research Group University of Bergen Norway

Centre of Cancer Biomarkers CCBIO Department of Clinical Science Precision Oncology Research Group University of Bergen Norway Department of Internal Medicine Haukeland University Hospital Bergen Norway

Clinic for Hematology University Hospital Sofia Bulgaria

Department of Clinical Medicine University of Bergen Norway Neuroimmunology Lab Haukeland University Hospital Bergen Norway

Department of Hemato Oncology Stavanger University Hospital Norway

Department of Hematology and Medical Oncology Universitätsklinikum Jena Germany

Department of Hematology and Oncology Innsbruck Medical University and Tyrolean Cancer Research Institute Innsbruck Austria

Department of Hematology and Oncology Innsbruck Medical University and Tyrolean Cancer Research Institute Innsbruck Austria Medical Clinic 3 Oncology Hematology and Rheumatology University Hospital Bonn Germany

Department of Hematology Institute of Hematology and Transfusion Medicine Warsaw Poland

Department of Hematology Medical University of Gdańsk Poland

Department of Hematology St Olavs Hospital Trondheim Norway IKM NTNU Trondheim Norway

Department of Hematology University Hospital Center Rebro Zagreb Croatia

Department of Hematology University Hospital Leuven Belgium

Department of Hematology VU University Medical Center Amsterdam the Netherlands

Department of Internal Medicine 4 Wels Grieskirchen Hospital Wels Austria

Department of Internal Medicine Hematology University Hospital Hradec Kralove Czech Republic

Department of Medicine Karolinska University Hospital Stockholm Sweden

Department of Medicine Oslo University Hospital Norway

Flow Cytometry Facility University of Zurich Switzerland

Hematology Department Cliniques Universitaires St Luc Brussels Belgium

Hematology Research Unit Helsinki University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center Department of Hematology Finland

Hematology Research Unit Helsinki University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center Department of Hematology Finland Department of Clinical Chemistry University of Helsinki Finland

Hematology Unit Aarhus University Hospital Denmark

Internal Medicine Hospital Feldkirch Austria

Mass Cytometry Facility University of Zurich Switzerland

NMDTI Robert H Lurie Comprehensive Cancer Center of Northwestern University Chicago IL USA

References provided by Crossref.org

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$a Monitoring of single cell signal transduction in leukemic cellular subsets has been proposed to provide deeper understanding of disease biology and prognosis, but has so far not been tested in a clinical trial of targeted therapy. We developed a complete mass cytometry analysis pipeline for characterization of intracellular signal transduction patterns in the major leukocyte subsets of chronic phase chronic myeloid leukemia. Changes in phosphorylated Bcr-Abl1 and the signaling pathways involved were readily identifiable in peripheral blood single cells already within three hours of the patient receiving oral nilotinib. The signal transduction profiles of healthy donors were clearly distinct from those of the patients at diagnosis. Furthermore, using principal component analysis, we could show that phosphorylated transcription factors STAT3 (Y705) and CREB (S133) within seven days reflected BCR-ABL1IS at three and six months. Analyses of peripheral blood cells longitudinally collected from patients in the ENEST1st clinical trial showed that single cell mass cytometry appears to be highly suitable for future investigations addressing tyrosine kinase inhibitor dosing and effect. (clinicaltrials.gov identifier: 01061177).
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$a Skavland, Jørn $u Centre of Cancer Biomarkers CCBIO, Department of Clinical Science, Precision Oncology Research Group, University of Bergen, Norway.
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$a Gavasso, Sonia $u Department of Clinical Medicine, University of Bergen, Norway. Neuroimmunology Lab, Haukeland University Hospital, Bergen, Norway.
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$a Tosevski, Vinko $u Mass Cytometry Facility, University of Zurich, Switzerland.
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$a Stentoft, Jesper $u Hematology Unit, Aarhus University Hospital, Denmark.
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$a Thaler, Josef $u Department of Internal Medicine IV, Wels-Grieskirchen Hospital, Wels, Austria.
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$a Thielen, Noortje $u Department of Hematology, VU University Medical Center, Amsterdam, the Netherlands.
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