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Insight Into How A Fusion Gene Promotes Childhood Leukemia

Date:
March 16, 2009
Source:
Journal of Clinical Investigation
Summary:
Fusion of the genes TEL and AML1 to form the TEL-AML1 fusion gene is a frequent genetic abnormality in childhood acute lymphoblastic leukemia. This mutation usually occurs before birth but can remain clinically silent for up to 15 years.
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Fusion of the genes TEL and AML1 to form the TEL-AML1 fusion gene is a frequent genetic abnormality in childhood acute lymphoblastic leukemia. This mutation usually occurs before birth but can remain clinically silent for up to 15 years.

Development of clinical leukemia requires the acquisition of one or more additional genetic mutations after birth, and previous studies have suggested that these mutations are linked to abnormal immune responses to infection.

Researchers have sought to determine why the TEL-AML1 fusion event shows no clinical effect for more than a decade, and what properties of the TEL-AML1 protein are involved in the acquisition of secondary genetic mutations and the development of clinical leukemia.

Mel Greaves and colleagues from the Institute of Cancer Research in the United Kingdom now report in the JCI that dysregulation of a signaling pathway involving the growth factor TGF-beta is a critical component of TEM-AML1 function. TGF-beta normally regulates cell differentiation and self-renewal as well as immune and inflammatory responses. These authors show that certain mouse cells expressing TEL-AML1 proliferate at a slower rate than their parent cells, but that these cells as well as human cord blood progenitor cells expressing TEL-AML1 have a marked growth advantage in the presence of TGF-beta, compared to normal cells.

These data suggest that loss of sensitivity to TGF-beta could be an important component of the function of TEL-AML1. The precise mechanism by which TEL-AML1 inhibits TGF-beta signaling is not yet clear, but the results of this study indicate that it involves TEL-AML1 binding to the TGF-beta target molecule Smad3.

Further studies will be required to determine how cells expressing TEL-AML1 may be further selected by immune or inflammatory reactions.


Story Source:

The above post is reprinted from materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal Reference:

  1. The TEL-AML1 leukemia fusion gene dysregulates the TGF-beta pathway in early B lineage progenitor cells. Journal of Clinical Investigation, March 16, 2009

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Journal of Clinical Investigation. "Insight Into How A Fusion Gene Promotes Childhood Leukemia." ScienceDaily. ScienceDaily, 16 March 2009. <www.sciencedaily.com/releases/2009/03/090316173309.htm>.
Journal of Clinical Investigation. (2009, March 16). Insight Into How A Fusion Gene Promotes Childhood Leukemia. ScienceDaily. Retrieved June 30, 2015 from www.sciencedaily.com/releases/2009/03/090316173309.htm
Journal of Clinical Investigation. "Insight Into How A Fusion Gene Promotes Childhood Leukemia." ScienceDaily. www.sciencedaily.com/releases/2009/03/090316173309.htm (accessed June 30, 2015).

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