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Found: Inherited Cause of Predisposition to DLBCL

doi: 10.1097/01.COT.0000437973.41434.13
Figure. Diff

Figure. Diff

New findings suggest that children with an inherited genetic defect in the interleukin-10 (IL-10) pathway have a genetic predisposition to some lymphomas, according to a study now available online ahead of print in Blood (doi: 10.1182/blood-2013-06-508267). Though it is known that chronic intestinal inflammation is a risk factor for cancer, this is the first research to show a link between the defect, very-early-onset inflammatory bowel disease (VEO-IBD), and cancer development in infants and children.

“When one VEO-IBD patient with an IL-10R deficiency developed diffuse large B-cell lymphoma, we suspected it might be an unfortunate circumstance. However, when the second, third, fourth, and fifth children were diagnosed, it was clear that this was not a chance occurrence,” lead study author Alain Fischer, MD, PhD, of the Imagine Institute, French National Institute of Health and Medical Research and Assistance Publique–Hôpitaux de Paris, said in a news release.

The study's researchers analyzed the molecular composition, chromosomal abnormalities, and genetic expression profiles of five children with the IL-10 deficiency between ages 5.5 and 6.5 being monitored for VEO-IBD at the Necker Children's Hospital in Paris and the Munich Children's Hospital. A genetic defect in IL-10 or one of its receptors (IL-10R1 or IL-10R2) turns off the pathway's normal protective function, which can result in the development of early onset inflammatory bowel disease.

The five children in the study had each developed highly proliferative and severe diffuse large B-cell lymphoma, which analyses showed were all of the same subtype. To confirm that an increased risk of lymphoma was not related to the immunosuppressive therapy that four of the five patients were receiving as treatment for IBD, the researchers found that of the 53 children being monitored for VEO-IBD at the Necker Children's Hospital and the Munich Children's Hospital who received the treatment, the patients with the IL-10 deficiency were the only ones who developed lymphoma.

Fischer said via email that he considers the findings to be conclusive in terms of confirming this genetic defect as a lymphoma risk factor. The next step, he said, is to determine the mechanism by which IL-10 is protective, and the hope is that can then lead to potentially new therapeutic options for patients with these lymphomas.



© 2013 by Lippincott Williams & Wilkins, Inc.
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