Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib
Stein-Erik Gullaksen, Jørn Skavland, Sonia Gavasso, Vinko Tosevski, Krzysztof Warzocha, Claudia Dumrese, Augustin Ferrant, Tobias Gedde-Dahl, Andrzej Hellmann, Jeroen Janssen, Boris Labar, Alois Lang, Waleed Majeed, Georgi Mihaylov, Jesper Stentoft, Leif Stenke, Josef Thaler, Noortje Thielen, Gregor Verhoef, Jaroslava Voglova, Gert Ossenkoppele, Andreas Hochhaus, Henrik Hjorth-Hansen, Satu Mustjoki, Sieghart Sopper, Francis Giles, Kimmo Porkka, Dominik Wolf, Bjørn Tore Gjertsen, Stein-Erik Gullaksen, Jørn Skavland, Sonia Gavasso, Vinko Tosevski, Krzysztof Warzocha, Claudia Dumrese, Augustin Ferrant, Tobias Gedde-Dahl, Andrzej Hellmann, Jeroen Janssen, Boris Labar, Alois Lang, Waleed Majeed, Georgi Mihaylov, Jesper Stentoft, Leif Stenke, Josef Thaler, Noortje Thielen, Gregor Verhoef, Jaroslava Voglova, Gert Ossenkoppele, Andreas Hochhaus, Henrik Hjorth-Hansen, Satu Mustjoki, Sieghart Sopper, Francis Giles, Kimmo Porkka, Dominik Wolf, Bjørn Tore Gjertsen
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-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).
Trial registration: ClinicalTrials.gov NCT01061177.
Copyright© 2017 Ferrata Storti Foundation.
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Source: PubMed