1: Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6068-73. Epub 2005 Apr 12. 

Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell
acute lymphoblastic leukemia.

Langenau DM, Feng H, Berghmans S, Kanki JP, Kutok JL, Look AT.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical
School, Boston, MA 02115, USA.

We have created a stable transgenic rag2-EGFP-mMyc zebrafish line that develops
GFP-labeled T cell acute lymphoblastic leukemia (T-ALL), allowing visualization
of the onset and spread of this disease. Here, we show that leukemias from this
transgenic line are highly penetrant and render animals moribund by 80.7 +/-
17.6 days of life (+/-1 SD, range = 50-158 days). These T cell leukemias are
clonally aneuploid, can be transplanted into irradiated recipient fish, and
express the zebrafish orthologues of the human T-ALL oncogenes tal1/scl and
lmo2, thus providing an animal model for the most prevalent molecular subgroup
of human T-ALL. Because T-ALL develops very rapidly in rag2-EGFP-mMyc transgenic
fish (in which "mMyc" represents mouse c-Myc), this line can only be maintained
by in vitro fertilization. Thus, we have created a conditional transgene in
which the EGFP-mMyc oncogene is preceded by a loxed dsRED2 gene and have
generated stable rag2-loxP-dsRED2-loxP-EGFP-mMyc transgenic zebrafish lines,
which have red fluorescent thymocytes and do not develop leukemia. Transgenic
progeny from one of these lines can be induced to develop T-ALL by injecting Cre
RNA into one-cell-stage embryos, demonstrating the utility of the Cre/lox system
in the zebrafish and providing an essential step in preparing this model for
chemical and genetic screens designed to identify modifiers of Myc-induced
T-ALL.

PMID: 15827121 [PubMed - indexed for MEDLINE]


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2: Blood. 2004 Apr 1;103(7):2530-40. Epub 2003 Dec 4. 

Differential gene expression of human stem progenitor cells derived from early
stages of in utero human hematopoiesis.

Shojaei F, Gallacher L, Bhatia M.

Robarts Research Institute, Stem Cell Biology and Regenerative Medicine, London,
ON, Canada.

Hematopoietic stem progenitor cells (HSPCs) are highly enriched in a rare subset
of Lin-CD34+CD38- cells. Independent of stage of human development, HSPC
function segregates to the subset of Lin-CD34+CD38- cells. However,
fetal-derived HSPCs demonstrate distinct self-renewal and differentiation
capacities compared with their adult counterparts. Here, to characterize the
molecular nature of fetal HSPCs, suppressive subtractive hybridization was used
to compare gene expression of HSPCs isolated from fetal blood (FB-HSPCs) versus
adult mobilized peripheral blood (MPB-HSPCs). We identified 97 differentially
expressed genes that could be annotated into distinct groups that include
transcription factors, cell cycle regulators, and genes involved in signal
transduction. Candidate regulators, such as Lim only domain-2 (LMO2), nuclear
factor-kappa B (NF-kappaB), tripartite motif 28 (Trim28), and N-myc
protooncogene (MYCN), and a novel homeobox gene product were among transcripts
that were found to be differentially expressed and could be associated with
specific proliferation and differentiation properties unique to FB-HSPCs.
Interestingly, the majority of genes associated with signal transduction belong
to Ras pathway, highlighting the significance of Ras signaling in FB-HSPCs.
Genes differentially expressed in FB-HSPCs versus adult MPB-HSPCs were verified
using quantitative real-time polymerase chain reaction (Q-PCR). This approach
also resulted in the identification of a transcript that is highly expressed in
FB-HSPCs but not detectable in more differentiated Lin-CD34+CD38+ FB
progenitors. Our investigation represents the first study to compare
phenotypically similar, but functionally distinct, HSPC populations and to
provide a gene profile of unique human HSPCs with higher proliferative capacity
derived from early in utero human blood development.

PMID: 14656878 [PubMed - indexed for MEDLINE]


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