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

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

Haematologica. 2017 May 18;:

Authors: Gullaksen SE, 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 BT

Abstract
Monitoring of single cell signal transduction in leukemic cellular subsets has been proposed to provide deeper understanding of disease biology and prognostication, 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 leukaemia. Changes in phosphorylated Bcr-Abl1 and its involved signalling pathways were readily identifiable in peripheral blood single cells already within 3 hours of per oral nilotinib dosing. The signal transduction profiles of healthy donors were clearly distinct from that of the patients at diagnosis. Furthermore, using principal component analysis we could show that phosphorylated transcription factors STAT3 (Y705) and CREB (S133) within 7 days reflected BCR-ABL1IS at 3 and 6 months. Analyses of peripheral blood cells longitudinally collected from ENEST1st clinical trial patients showed that single cell mass cytometry appears highly suitable for future investigations addressing tyrosine kinase inhibitor dosing and effect. (clinicaltrials.gov Identifier:NCT01061177).

PMID: 28522574 [PubMed - as supplied by publisher]

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