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

被引：25

作者：

Gullaksen, Stein-Erik ^{[1
]}

Skavland, Jorn ^{[1
]}

Gavasso, Sonia ^{[2
,3
]}

Tosevski, Vinko ^{[4
]}

Warzocha, Krzysztof ^{[5
]}

Dumrese, Claudia ^{[6
]}

Ferrant, Augustin ^{[7
]}

Gedde-Dahl, Tobias ^{[8
]}

Hellmann, Andrzej ^{[9
]}

Janssen, Jeroen ^{[10
]}

Labar, Boris ^{[11
]}

Lang, Alois ^{[12
]}

Majeed, Waleed ^{[13
]}

Mihaylov, Georgi ^{[14
]}

Stentoft, Jesper ^{[15
]}

Stenke, Leif ^{[16
]}

Thaler, Josef ^{[17
]}

Thielen, Noortje ^{[10
]}

Verhoef, Gregor ^{[18
]}

Voglova, Jaroslava ^{[19
]}

Ossenkoppele, Gert ^{[10
]}

Hochhaus, Andreas ^{[20
]}

Hjorth-Hansen, Henrik ^{[21
,22
]}

Mustjoki, Satu ^{[23
,24
,25
]}

Sopper, Sieghart ^{[26
,27
]}

Giles, Francis ^{[28
]}

Porkka, Kimmo ^{[23
,24
]}

Wolf, Dominik ^{[26
,27
,29
]}

Gjertsen, Bjorn Tore ^{[1
,30
]}

机构：

[1] Univ Bergen, Dept Clin Sci, Precis Oncol Res Grp, Ctr Canc Biomarkers CCBIO, Bergen, Norway

[2] Univ Bergen, Dept Clin Med, Bergen, Norway

[3] Haukeland Hosp, Neuroimmunol Lab, Bergen, Norway

[4] Univ Zurich, Mass Cytometry Facil, Zurich, Switzerland

[5] Inst Hematol & Transfus Med, Dept Hematol, Warsaw, Poland

[6] Univ Zurich, Flow Cytometry Facil, Zurich, Switzerland

[7] Clin Univ St Luc, Dept Hematol, Brussels, Belgium

[8] Oslo Univ Hosp, Dept Med, Oslo, Norway

[9] Med Univ Gdansk, Dept Hematol, Gdansk, Poland

[10] Vrije Univ Amsterdam Med Ctr, Dept Hematol, Amsterdam, Netherlands

[11] Univ Hosp Ctr Rebro, Dept Hematol, Zagreb, Croatia

[12] Hosp Feldkirch, Internal Med, Feldkirch, Austria

[13] Stavanger Univ Hosp, Dept Hematooncol, Stavanger, Norway

[14] Univ Hosp Sofia, Clin Hematol, Sofia, Bulgaria

[15] Aarhus Univ Hosp, Hematol Unit, Aarhus, Denmark

[16] Karolinska Univ Hosp, Dept Med, Stockholm, Sweden

[17] Wels Grieskirchen Hosp, Dept Internal Med 4, Wels, Austria

[18] Univ Hosp Leuven, Dept Hematol, Leuven, Belgium

[19] Univ Hosp Hradec Kralove, Dept Internal Med Hematol 4, Hradec Kralove, Czech Republic

[20] Univ Klinikum Jena, Dept Hematol & Med Oncol, Jena, Germany

[21] St Olavs Hosp, Dept Hematol, Trondheim, Norway

[22] NTNU, IKM, Trondheim, Norway

[23] Univ Helsinki, Hematol Res Unit Helsinki, Helsinki, Finland

[24] Helsinki Univ Hosp, Ctr Comprehens Canc, Dept Hematol, Helsinki, Finland

[25] Univ Helsinki, Dept Clin Chem, Helsinki, Finland

[26] Innsbruck Med Univ, Dept Hematol & Oncol, Innsbruck, Austria

[27] Tyrolean Canc Res Inst, Innsbruck, Austria

[28] Northwestern Univ, NMDTI, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

[29] Univ Hosp Bonn UKB, Med Clin Oncol Hematol & Rheumatol 3, Bonn, Germany

[30] Haukeland Hosp, Dept Internal Med, Bergen, Norway

来源：

HAEMATOLOGICA | 2017年 / 102卷 / 08期

关键词：

CHRONIC MYELOGENOUS LEUKEMIA; KINASE INHIBITOR THERAPY; BCR-ABL; MOLECULAR RESPONSE; IMATINIB; PHOSPHOPROTEIN; ACTIVATION; REGULATORS; DASATINIB; CORRELATE;

D O I：

10.3324/haematol.2017.167080

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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)

引用

页码：1361 / 1367

页数：7

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