Defining the in vivo characteristics of acute myeloid leukemia cells behavior by intravital imaging
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The majority of acute myeloid leukemia (AML) patients have a poor response to conventional chemotherapy. The survival of chemoresistant cells is thought to depend on leukemia-bone marrow (BM) microenvironment interactions, which are not well understood. The CXCL12/CXCR4 axis has been proposed to support AML growth but was not studied at the single AML cell level. We recently showed that T-cell acute lymphoblastic leukemia (T-ALL) cells are highly motile in the BM; however, the characteristics of AML cell migration within the BM remain undefined. Here, we characterize the in vivo migratory behavior of AML cells and their response to chemotherapy and CXCR4 antagonism, using high-resolution 2-photon and confocal intravital microscopy of mouse calvarium BM and the well-established MLL-AF9-driven AML mouse model. We used the Notch1-driven T-ALL model as a benchmark comparison and AMD3100 for CXCR4 antagonism experiments. We show that AML cells are migratory, and in contrast with T-ALL, chemoresistant AML cells become less motile. Moreover, and in contrast with T-ALL, the in vivo exploratory behavior of expanding and chemoresistant AML cells is unaffected by AMD3100. These results expand our understanding of AML cells-BM microenvironment interactions, highlighting unique traits of leukemia of different lineages.
Date Issued
2019-02-01
Date Acceptance
2018-11-08
Citation
Immunology and Cell Biology, 2019, 97 (2), pp.229-235
ISSN
0818-9641
Publisher
Wiley
Start Page
229
End Page
235
Journal / Book Title
Immunology and Cell Biology
Volume
97
Issue
2
Copyright Statement
© 2018 The Authors Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Immunology Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor
Human Frontier Science Program
Bloodwise
Commission of the European Communities
European Hematology Association
Biotechnology and Biological Sciences Research Council (BBSRC)
Blood Cancer UK
Biotechnology and Biological Sciences Research Council (BBSRC)
Cancer Research UK
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30422351
Grant Number
rgp0051/2011
12033
337066
n/a
BB/L023776/1
15031
BB/I004033/1
11831
Subjects
Acute myeloid leukemia cells
chemokines
intravital imaging
lymphoblastic leukemia
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-11-13