home   genetic news   bioinformatics   biotechnology   literature   journals   ethics   positions   events   sitemap
  HUM-MOLGEN -> Genetic News | search  

A triggering event is identified in the transformation of a precancerous cell to a cancer stem cell

  January, 23 2008 8:08
your information resource in human molecular genetics
Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia. Hong, D., Gupta, R., Ancliff, P., et al. Science, 319, 336-339 (January 18, 2008).

Acute lymphoblastic leukemia (ALL), which strikes during childhood, is often associated with a chromosomal translocation that creates the TEL-AML1 fusion gene. This event, which primarily occurs in utero, gives rise to a preleukemic clone that has been believed to convert to a self-renewing leukemic cell line.

The present study first focused on a rare population of CD34+CD38(-/low)CD19+ cells isolated from TEL-AML1-positive ALL patients. Their leukemogenic potential was demonstrated via engraftment into nonobese diabetic, severe combined immunodeficient (NOD/SCID) mice. Secondary grafts were also successful, indicating that the CD34+CD38(-/low)CD19+ cells are self-renewing cancer stem cells.

The events that transpire between creation of the TEL-AML1 fusion gene and transformation into leukemic stem cells was investigated in monochorionic twins, since these embryos share a placenta that may permit the migration of a preleukemic clone from one to the other. A pair of twins was identified in which one child developed leukemia at the age of two, while the other remained healthy. The peripheral blood of the healthy child contained a population of CD34+CD38(-/low)CD19+ cells at a very low frequency (0.002% of total mononuclear cells). Progenitor B cells did not experess TEL-AML1 transcripts, nor did more primitive multipotent stem cells that also did not express the B-lineage marker CD19. An analysis of IgH gene rearrangements of the healthy twin’s CD34+CD38(-low)CD19+ cells suggested that they were a clonally expanded population and that the fusion gene arose or had first functional impact in a cell that had already undergone recombination at the diversity and joining loci of the IgH gene. An analysis of the leukemic child’s CD34+CD38(-/low)CD19+ cells suggested that they were a descendent of the similar cells found in the healthy child.

A xenograft model was create by transplanting TEL-AML1 transduced human cord blood cells into NOD/SCID mice. The CD34+CD38(-/low)CD19+ cells displayed diversity and joining loci rearrangements in the IgH gene, but did not express CD10, thus resembling cells isolated from the healthy twin. They demonstrated self-renewal potential in vitro and engrafted in NOD/SCID mice, while also giving rise to more mature B cells (CD38+CD19+). The TEL-AML1-generated CD34+CD38(-/low)CD19+ cells have the capacity for self-renewal in vivo, suggesting that the fusion gene is sufficient to generate preleukemic stem cells.

This research has created a xenograft model that may serve as a tool for further examination of genetic alterations cooperating with the TEL-AML1 fusion gene. And the results offer an explanation of how surviving preleukemic stem cells may cause a relapse in a patient whose disease appeared to have been successfully treated.

Message posted by: Keith Markey

print this article mail this article
Bookmark and Share this page (what is this?)

Social bookmarking allows users to save and categorise a personal collection of bookmarks and share them with others. This is different to using your own browser bookmarks which are available using the menus within your web browser.

Use the links below to share this article on the social bookmarking site of your choice.

Read more about social bookmarking at Wikipedia - Social Bookmarking

Latest News
Variants Associated with Pediatric Allergic Disorder

Mutations in PHF6 Found in T-Cell Leukemia

Genetic Risk Variant for Urinary Bladder Cancer

Antibody Has Therapeutic Effect on Mice with ALS

Regulating P53 Activity in Cancer Cells

Anti-RNA Therapy Counters Breast Cancer Spread

Mitochondrial DNA Diversity

The Power of RNA Sequencing

‘Pro-Ageing' Therapy for Cancer?

Niche Genetics Influence Leukaemia

Molecular Biology: Clinical Promise for RNA Interference

Chemoprevention Cocktail for Colon Cancer

more news ...

Generated by News Editor 2.0 by Kai Garlipp
WWW: Kai Garlipp, Frank S. Zollmann.
7.0 © 1995-2017 HUM-MOLGEN. All rights reserved. Liability, Copyright and Imprint.