In vivo monitoring of leukemia-niche interactions in a zebrafish xenograft model.

Acute lymphoblastic leukemia (ALL) is the most common type of malignancy in children. ALL prognosis after initial diagnosis is generally good; however, patients suffering from relapse have a poor outcome. The tumor microenvironment is recognized as an important contributor to relapse, yet the cell-c...

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Main Authors: Anja Arner, Andreas Ettinger, Bradley Wayne Blaser, Bettina Schmid, Irmela Jeremias, Nadia Rostam, Vera Binder-Blaser
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0309415
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author Anja Arner
Andreas Ettinger
Bradley Wayne Blaser
Bettina Schmid
Irmela Jeremias
Nadia Rostam
Vera Binder-Blaser
author_facet Anja Arner
Andreas Ettinger
Bradley Wayne Blaser
Bettina Schmid
Irmela Jeremias
Nadia Rostam
Vera Binder-Blaser
author_sort Anja Arner
collection DOAJ
description Acute lymphoblastic leukemia (ALL) is the most common type of malignancy in children. ALL prognosis after initial diagnosis is generally good; however, patients suffering from relapse have a poor outcome. The tumor microenvironment is recognized as an important contributor to relapse, yet the cell-cell interactions involved are complex and difficult to study in traditional experimental models. In the present study, we established an innovative larval zebrafish xenotransplantation model, that allows the analysis of leukemic cells (LCs) within an orthotopic niche using time-lapse microscopic and flow cytometric approaches. LCs homed, engrafted and proliferated within the hematopoietic niche at the time of transplant, the caudal hematopoietic tissue (CHT). A specific dissemination pattern of LCs within the CHT was recorded, as they extravasated over time and formed clusters close to the dorsal aorta. Interactions of LCs with macrophages and endothelial cells could be quantitatively characterized. This zebrafish model will allow the quantitative analysis of LCs in a functional and complex microenvironment, to study mechanisms of niche mediated leukemogenesis, leukemia maintenance and relapse development.
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spelling doaj-art-17ad6fb7b0134e96acfb19449f186da92025-01-18T05:31:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01198e030941510.1371/journal.pone.0309415In vivo monitoring of leukemia-niche interactions in a zebrafish xenograft model.Anja ArnerAndreas EttingerBradley Wayne BlaserBettina SchmidIrmela JeremiasNadia RostamVera Binder-BlaserAcute lymphoblastic leukemia (ALL) is the most common type of malignancy in children. ALL prognosis after initial diagnosis is generally good; however, patients suffering from relapse have a poor outcome. The tumor microenvironment is recognized as an important contributor to relapse, yet the cell-cell interactions involved are complex and difficult to study in traditional experimental models. In the present study, we established an innovative larval zebrafish xenotransplantation model, that allows the analysis of leukemic cells (LCs) within an orthotopic niche using time-lapse microscopic and flow cytometric approaches. LCs homed, engrafted and proliferated within the hematopoietic niche at the time of transplant, the caudal hematopoietic tissue (CHT). A specific dissemination pattern of LCs within the CHT was recorded, as they extravasated over time and formed clusters close to the dorsal aorta. Interactions of LCs with macrophages and endothelial cells could be quantitatively characterized. This zebrafish model will allow the quantitative analysis of LCs in a functional and complex microenvironment, to study mechanisms of niche mediated leukemogenesis, leukemia maintenance and relapse development.https://doi.org/10.1371/journal.pone.0309415
spellingShingle Anja Arner
Andreas Ettinger
Bradley Wayne Blaser
Bettina Schmid
Irmela Jeremias
Nadia Rostam
Vera Binder-Blaser
In vivo monitoring of leukemia-niche interactions in a zebrafish xenograft model.
PLoS ONE
title In vivo monitoring of leukemia-niche interactions in a zebrafish xenograft model.
title_full In vivo monitoring of leukemia-niche interactions in a zebrafish xenograft model.
title_fullStr In vivo monitoring of leukemia-niche interactions in a zebrafish xenograft model.
title_full_unstemmed In vivo monitoring of leukemia-niche interactions in a zebrafish xenograft model.
title_short In vivo monitoring of leukemia-niche interactions in a zebrafish xenograft model.
title_sort in vivo monitoring of leukemia niche interactions in a zebrafish xenograft model
url https://doi.org/10.1371/journal.pone.0309415
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