Oncotarget

Research Papers:

Flow cytometric characterization of acute leukemia reveals a distinctive “blast gate” of murine T-lymphoblastic leukemia/lymphoma

Zengkai Pan, Min Yang, Kezhi Huang, Guntram Büsche, Silke Glage, Arnold Ganser and Zhixiong Li _

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Oncotarget. 2018; 9:2320-2328. https://doi.org/10.18632/oncotarget.23410

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Abstract

Zengkai Pan1,*, Min Yang1,*, Kezhi Huang1,2,*, Guntram Büsche3, Silke Glage4, Arnold Ganser1 and Zhixiong Li1

1Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

2Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

3Institute of Pathology, Hannover Medical School, Hannover, Germany

4Institute of Laboratory Animal Science, Hannover Medical School, Hannover, Germany

*These authors have contributed equally to this work

Correspondence to:

Zhixiong Li, email: li.zhixiong@mh-hannover.de

Keywords: flow cytometry; T-ALL; blast gate; midostaurin; FLT3-ITD

Received: September 05, 2017    Accepted: December 05, 2017    Published: December 18, 2017

ABSTRACT

Immunophenotypic analysis using multiparameter flow cytometry is an indispensable tool for diagnosis and management of acute leukemia. Mouse models have been widely used for medical research for more than 100 years and are indispensable for leukemia research. However, immunophenotypic analysis of murine leukemia was not always performed in published studies, and blast gating for isolation of blasts was shown only in very few studies. No systemic characterization of all types of murine acute leukemia in large cohorts by flow cytometry has been reported. In this study, we used flow cytometry to comprehensively characterize murine acute leukemia in a large cohort of mice. We found that murine T-lymphoblastic leukemia/lymphoma (T-ALL) exhibits a distinctive “blast gate” (CD45bright) with CD45/side scatter gating that differs from the “blast gate” (CD45dim) of human T-ALL. By contrast, murine B-lymphoblastic leukemia and acute myeloid leukemia show the same blast region (CD45dim) as human leukemia. Using blast cell gating, we for first time detected T-ALL development in FLT3-ITD knock-in mice (incidence: 23%). These leukemic cells were selectively killed by the FLT3 inhibitors crenolanib and midostaurin in vitro. These data suggest that FLT3-ITD plays a potential role in the pathogenesis of T-ALL and that FLT3-ITD inhibition is a therapeutic option in the management of patients with T-ALL. Our gating strategy for immunophenotypic analysis can be used for leukemogenesis and preclinical gene therapy studies in mice and may improve the quality of such analyses.


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