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

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http://hdl.handle.net/10138/212972

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Gullaksen , S-E , Skavland , J , Gavasso , S , Tosevski , V , Warzocha , K , Dumrese , C , Ferrant , A , Gedde-Dahl , T , Hellmann , A , Janssen , J , Labar , B , Lang , A , Majeed , W , Mihaylov , G , Stentoft , J , Stenke , L , Thaler , J , Thielen , N , Verhoef , G , Voglova , J , Ossenkoppele , G , Hochhaus , A , Hjorth-Hansen , H , Mustjoki , S , Sopper , S , Giles , F , Porkka , K , Wolf , D & Gjertsen , B T 2017 , ' Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib ' , Haematologica , vol. 102 , no. 8 , pp. 1361-1367 . https://doi.org/10.3324/haematol.2017.167080

Title: Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib
Author: Gullaksen, Stein-Erik; Skavland, Jorn; Gavasso, Sonia; Tosevski, Vinko; Warzocha, Krzysztof; Dumrese, Claudia; Ferrant, Augustin; Gedde-Dahl, Tobias; Hellmann, Andrzej; Janssen, Jeroen; Labar, Boris; Lang, Alois; Majeed, Waleed; Mihaylov, Georgi; Stentoft, Jesper; Stenke, Leif; Thaler, Josef; Thielen, Noortje; Verhoef, Gregor; Voglova, Jaroslava; Ossenkoppele, Gert; Hochhaus, Andreas; Hjorth-Hansen, Henrik; Mustjoki, Satu; Sopper, Sieghart; Giles, Francis; Porkka, Kimmo; Wolf, Dominik; Gjertsen, Bjorn Tore
Contributor: University of Helsinki, Medicum
University of Helsinki, Clinicum
Date: 2017-08
Language: eng
Number of pages: 7
Belongs to series: Haematologica
ISSN: 0390-6078
URI: http://hdl.handle.net/10138/212972
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(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)
Subject: CHRONIC MYELOGENOUS LEUKEMIA
KINASE INHIBITOR THERAPY
BCR-ABL
MOLECULAR RESPONSE
IMATINIB
PHOSPHOPROTEIN
ACTIVATION
REGULATORS
DASATINIB
CORRELATE
3122 Cancers
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