Featured Research

from universities, journals, and other organizations

Why Gene Therapy Caused Leukemia In Some 'Boy In The Bubble Syndrome' Patients

Date:
August 10, 2008
Source:
Journal of Clinical Investigation
Summary:
Severe combined immunodeficiency (SCID), sometimes called 'Boy in the bubble syndrome', is a genetic disorder in which the patient lacks most types of immune cell. Almost 10 years ago, two independent groups used gene therapy to treat a few infants with the most common form of SCID, SCID-X1, which is caused by mutations in the IL2RG gene.

Severe combined immunodeficiency (SCID), sometimes called 'Boy in the bubble syndrome', is a genetic disorder in which the patient lacks most types of immune cell. Almost 10 years ago, two independent groups (one in London, United Kingdom, and one in Paris, France) used gene therapy to treat a few infants with the most common form of SCID, SCID-X1, which is caused by mutations in the IL2RG gene.

Although most infants showed dramatic improvement following gene therapy, 4 of the 9 infants that were successfully treated in Paris developed leukemia between 3 and 6 years after the treatment. The groups in London and Paris had used very similar gene therapy approaches and until now it was not clear why leukemia was detected only in some of the infants treated in Paris. However, Adrian Thrasher and colleagues, at the Institute for Child Health, London, now report that 1 of the infants successfully treated in London also developed a form of leukemia known as T cell acute lymphoblastic leukemia (T-ALL).

In the study, Thrasher and colleagues go on to show why that infant developed leukemia. During gene therapy, the correct form of the IL2RG gene and the vector that carried this into the cells integrated into part of the genome that contained a gene known as LMO2 and activated this gene. In combination with other genetic mutations that were not caused by the gene therapy (including activation of the NOTCH1 gene, deletion of the CDKN2A gene locus, and translocation of the TCRb gene into the SIL-TAL1 locus), this caused the development of leukemia.

In a related paper by Salima Hacein-Bey-Abina and colleagues, the researchers in Paris who performed the other gene therapy trial have now identified similar reasons to explain why 2 of the 4 infants that developed leukemia became sick. In one patient, the gene and vector integrated into the part of the genome that contained LMO2 and activated the gene, and in the other patient, the gene and vector integrated into part of the genome that contained a gene known as CCND2 and activated this gene.

In both infants, other genetic mutations not caused by the gene therapy contributed to the development of leukemia and these mutations were very similar to those observed in the patient treated in London (activation of the NOTCH1 gene, deletion of the CDKN2A gene locus, and rearrangement of the SIL-TAL1 locus).

The authors of both studies hope that these data provide insight that will help in the design of future gene therapy protocols to ensure similar efficacy but decreased toxicity.


Story Source:

The above story is based on materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hacein-Bey-Abina et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. Journal of Clinical Investigation, 2008; DOI: 10.1172/JCI35700

Cite This Page:

Journal of Clinical Investigation. "Why Gene Therapy Caused Leukemia In Some 'Boy In The Bubble Syndrome' Patients." ScienceDaily. ScienceDaily, 10 August 2008. <www.sciencedaily.com/releases/2008/08/080807175438.htm>.
Journal of Clinical Investigation. (2008, August 10). Why Gene Therapy Caused Leukemia In Some 'Boy In The Bubble Syndrome' Patients. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2008/08/080807175438.htm
Journal of Clinical Investigation. "Why Gene Therapy Caused Leukemia In Some 'Boy In The Bubble Syndrome' Patients." ScienceDaily. www.sciencedaily.com/releases/2008/08/080807175438.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Microneedle Patch Promises Painless Pricks

Microneedle Patch Promises Painless Pricks

Reuters - Innovations Video Online (Oct. 18, 2014) Researchers at The National University of Singapore have invented a new microneedle patch that could offer a faster and less painful delivery of drugs such as insulin and painkillers. Video provided by Reuters
Powered by NewsLook.com
Raw: Nurse Nina Pham Arrives in Maryland

Raw: Nurse Nina Pham Arrives in Maryland

AP (Oct. 17, 2014) The first nurse to be diagnosed with Ebola at a Dallas hospital walked down the stairs of an executive jet into an ambulance at an airport in Frederick, Maryland, on Thursday. Pham will be treated at the National Institutes of Health. (Oct. 16) Video provided by AP
Powered by NewsLook.com
Raw: Cruise Ship Returns to US Over Ebola Fears

Raw: Cruise Ship Returns to US Over Ebola Fears

AP (Oct. 17, 2014) A Caribbean cruise ship carrying a Dallas health care worker who is being monitored for signs of the Ebola virus is heading back to Texas, US, after being refused permission to dock in Cozumel, Mexico. (Oct. 17) Video provided by AP
Powered by NewsLook.com
Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

AFP (Oct. 17, 2014) All four suspected Ebola cases admitted to hospitals in Spain on Thursday have tested negative for the deadly virus in a first round of tests, the government said Friday. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins