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

Haematologica
Stein-Erik GullaksenBjorn 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).

Citations

Nov 16, 2017·Blood·Elodie GrockowiakVéronique Maguer-Satta
Oct 20, 2018·The Analyst·Lei YinJingkai Gu
Jan 17, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Maria OmslandBjørn Tore Gjertsen
Feb 15, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Susann WinterUwe Platzbecker
Oct 23, 2018·Case Reports in Hematology·Håkon ReikvamBjørn Tore Gjertsen
Nov 24, 2020·European Journal of Immunology·Silje Michelsen SolbergSilke Appel
Aug 22, 2017·Molecular Aspects of Medicine·Lili WangCatherine J Wu

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flow cytometry
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