Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib
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 characte...
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| Published in | Haematologica (Roma) Vol. 102; no. 8; pp. 1361 - 1367 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Italy
Ferrata Storti Foundation
01.08.2017
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| Abstract | 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-ABL1
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. (
). |
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| AbstractList | 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) 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-ABL1 IS 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 ) 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-ABL1 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. ( ). |
| Author | Janssen, Jeroen Lang, Alois Porkka, Kimmo Labar, Boris Mustjoki, Satu Skavland, Jørn Gavasso, Sonia Giles, Francis Gedde-Dahl, Tobias Verhoef, Gregor Majeed, Waleed Thielen, Noortje Gullaksen, Stein-Erik Stenke, Leif Gjertsen, Bjørn Tore Thaler, Josef Ossenkoppele, Gert Hjorth-Hansen, Henrik Warzocha, Krzysztof Ferrant, Augustin Hellmann, Andrzej Stentoft, Jesper Hochhaus, Andreas Tosevski, Vinko Dumrese, Claudia Voglova, Jaroslava Sopper, Sieghart Wolf, Dominik Mihaylov, Georgi |
| AuthorAffiliation | 4 Mass Cytometry Facility, University of Zurich, Switzerland 24 Department of Clinical Chemistry, University of Helsinki, Finland 15 Hematology Unit, Aarhus University Hospital, Denmark 5 Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland 28 Department of Internal Medicine, Haukeland University Hospital, Bergen, Norway 11 Department of Hematology, University Hospital Center Rebro, Zagreb, Croatia 18 Department of Hematology, University Hospital Leuven, Belgium 1 Centre of Cancer Biomarkers CCBIO, Department of Clinical Science, Precision Oncology Research Group, University of Bergen, Norway 9 Department of Hematology, Medical University of Gdańsk, Poland 25 Department of Hematology and Oncology, Innsbruck Medical University and Tyrolean Cancer Research Institute, Innsbruck, Austria 13 Department of Hemato-Oncology, Stavanger University Hospital, Norway 7 Hematology Department, Cliniques Universitaires St Luc, Brussels, Belgium 12 Internal Medicine, Hospital |
| AuthorAffiliation_xml | – name: 17 Department of Internal Medicine IV, Wels-Grieskirchen Hospital, Wels, Austria – name: 23 Hematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Department of Hematology, Finland – name: 27 Medical Clinic 3, Oncology, Hematology and Rheumatology, University Hospital Bonn (UKB), Germany – name: 7 Hematology Department, Cliniques Universitaires St Luc, Brussels, Belgium – name: 15 Hematology Unit, Aarhus University Hospital, Denmark – name: 6 Flow Cytometry Facility, University of Zurich, Switzerland – name: 14 Clinic for Hematology, University Hospital Sofia, Bulgaria – name: 12 Internal Medicine, Hospital Feldkirch, Austria – name: 18 Department of Hematology, University Hospital Leuven, Belgium – name: 26 NMDTI, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA – name: 1 Centre of Cancer Biomarkers CCBIO, Department of Clinical Science, Precision Oncology Research Group, University of Bergen, Norway – name: 16 Department of Medicine, Karolinska University Hospital, Stockholm, Sweden – name: 10 Department of Hematology, VU University Medical Center, Amsterdam, the Netherlands – name: 19 4 th Department of Internal Medicine – Hematology, University Hospital Hradec Kralove, Czech Republic – name: 24 Department of Clinical Chemistry, University of Helsinki, Finland – name: 22 IKM, NTNU, Trondheim, Norway – name: 3 Neuroimmunology Lab, Haukeland University Hospital, Bergen, Norway – name: 11 Department of Hematology, University Hospital Center Rebro, Zagreb, Croatia – name: 21 Department of Hematology, St Olavs Hospital, Trondheim, Norway – name: 20 Department of Hematology and Medical Oncology, Universitätsklinikum Jena, Germany – name: 8 Department of Medicine, Oslo University Hospital, Norway – name: 9 Department of Hematology, Medical University of Gdańsk, Poland – name: 28 Department of Internal Medicine, Haukeland University Hospital, Bergen, Norway – name: 5 Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland – name: 13 Department of Hemato-Oncology, Stavanger University Hospital, Norway – name: 2 Department of Clinical Medicine, University of Bergen, Norway – name: 4 Mass Cytometry Facility, University of Zurich, Switzerland – name: 25 Department of Hematology and Oncology, Innsbruck Medical University and Tyrolean Cancer Research Institute, Innsbruck, Austria |
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| SubjectTerms | Cyclic AMP Response Element-Binding Protein - metabolism Fusion Proteins, bcr-abl - metabolism Humans Leukemia, Myeloid, Chronic-Phase - drug therapy Leukemia, Myeloid, Chronic-Phase - pathology Leukocytes - metabolism Medicin och hälsovetenskap Phosphorylation Protein-Tyrosine Kinases - therapeutic use Pyrimidines - pharmacology Pyrimidines - therapeutic use Signal Transduction - drug effects Signal Transduction - immunology Single-Cell Analysis - methods STAT3 Transcription Factor - metabolism |
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| Title | Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib |
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