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High-throughput cell transplantation establishes that tumor-initiating cells are abundant in zebrafish T-cell acute lymphoblastic leukemia.

Abstract：

:Self-renewal is a feature of cancer and can be assessed by cell transplantation into immune-compromised or immune-matched animals. However, studies in zebrafish have been severely limited by lack of these reagents. Here, Myc-induced T-cell acute lymphoblastic leukemias (T-ALLs) have been made in syngeneic, clonal zebrafish and can be transplanted into sibling animals without the need for immune suppression. These studies show that self-renewing cells are abundant in T-ALL and comprise 0.1% to 15.9% of the T-ALL mass. Large-scale single-cell transplantation experiments established that T-ALLs can be initiated from a single cell and that leukemias exhibit wide differences in tumor-initiating potential. T-ALLs also can be introduced into clonal-outcrossed animals, and T-ALLs arising in mixed genetic backgrounds can be transplanted into clonal recipients without the need for major histocompatibility complex matching. Finally, high-throughput imaging methods are described that allow large numbers of fluorescent transgenic animals to be imaged simultaneously, facilitating the rapid screening of engrafted animals. Our experiments highlight the large numbers of zebrafish that can be experimentally assessed by cell transplantation and establish new high-throughput methods to functionally interrogate gene pathways involved in cancer self-renewal.

journal_name

Blood

journal_title

Blood

authors

Smith AC,Raimondi AR,Salthouse CD,Ignatius MS,Blackburn JS,Mizgirev IV,Storer NY,de Jong JL,Chen AT,Zhou Y,Revskoy S,Zon LI,Langenau DM

doi

10.1182/blood-2009-10-246488

subject

Has Abstract

pub_date

2010-04-22 00:00:00

pages

3296-303

issue

16

eissn

0006-4971

issn

1528-0020

pii

blood-2009-10-246488

journal_volume

115

pub_type

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