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Defining the in vivo characteristics of acute myeloid leukemia cells behavior by intravital imaging

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Title: Defining the in vivo characteristics of acute myeloid leukemia cells behavior by intravital imaging
Authors: Duarte, D
Amarteifio, S
Ang, H
Kong, IY
Ruivo, N
Pruessner, G
Hawkins, ED
Lo Celso, C
Item 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.
Issue Date: 1-Feb-2019
Date of Acceptance: 8-Nov-2018
URI: http://hdl.handle.net/10044/1/66316
DOI: 10.1111/imcb.12216
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/Funder: 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
Funder's Grant Number: rgp0051/2011
12033
337066
n/a
BB/L023776/1
15031
BB/I004033/1
11831
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Immunology
Acute myeloid leukemia cells
chemokines
intravital imaging
lymphoblastic leukemia
PLUS G-CSF
CXCR4
CHEMOTHERAPY
CHEMOSENSITIZATION
MOBILIZATION
INHIBITION
PROGENITOR
Acute myeloid leukemia cells
chemokines
intravital imaging
lymphoblastic leukemia
Animals
Antineoplastic Agents
Bone Marrow
Cell Line, Tumor
Cell Movement
Chemokine CXCL12
Drug Resistance, Neoplasm
Heterocyclic Compounds
Intravital Microscopy
Leukemia, Myeloid, Acute
Mice
Microscopy, Confocal
Microscopy, Fluorescence, Multiphoton
Receptors, CXCR4
Tumor Microenvironment
Cell Line, Tumor
Bone Marrow
Animals
Mice
Heterocyclic Compounds
Receptors, CXCR4
Antineoplastic Agents
Microscopy, Confocal
Microscopy, Fluorescence, Multiphoton
Cell Movement
Drug Resistance, Neoplasm
Leukemia, Myeloid, Acute
Chemokine CXCL12
Tumor Microenvironment
Intravital Microscopy
Acute myeloid leukemia cells
chemokines
intravital imaging
lymphoblastic leukemia
0601 Biochemistry and Cell Biology
1107 Immunology
Immunology
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-11-13
Appears in Collections:Mathematics
Applied Mathematics and Mathematical Physics
Faculty of Natural Sciences