Česká Genetická Banka

NATURE: 28. 9. - 4. 10. 2012

Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics

"Burkitt’s lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL in developing countries, necessitating new strategies1. The normal germinal centre B cell is the presumed cell of origin for both BL and diffuse large B-cell lymphoma (DLBCL), yet gene expression analysis suggests that these malignancies may use different oncogenic pathways2. BL is subdivided into a sporadic subtype that is diagnosed in developed countries, the Epstein–Barr-virus-associated endemic subtype, and an HIV-associated subtype, but it is unclear whether these subtypes use similar or divergent oncogenic mechanisms. Here we used high-throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways in BL that cooperate with MYC, the defining oncogene of this cancer. In 70% of sporadic BL cases, mutations affecting the transcription factor TCF3 (E2A) or its negative regulator ID3 fostered TCF3 dependency. TCF3 activated the pro-survival phosphatidylinositol-3-OH kinase pathway in BL, in part by augmenting tonic B-cell receptor signalling. In 38% of sporadic BL cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. These findings suggest opportunities to improve therapy for patients with BL."

http://www.nature.com/nature/journal/v490/n7418/full/nature11378.html

Immunology: Tolerating pregnancy

"The activity of specific suppressive immune cells, some of which persist to aid subsequent pregnancies, helps to explain how a pregnant female's immune system tolerates fetal antigens inherited from the father."

http://www.nature.com/nature/journal/v490/n7418/full/490047a.html

Science: Intestinal Wound Healing Requires a Wnt Balancing Act

"Inflammatory bowel disease (IBD) encompasses a group of disorders of the colon and small intestine including Crohn's disease and ulcerative colitis. It affects roughly 396 per 100,000 persons worldwide (1) and in the United States is responsible for more than $1.7 billion in overall health care costs. The chronic or recurrent inflammation associated with this disease causes severe damage to the epithelial lining of the intestine. On page 108 of this issue, Miyoshi et al. (2) present a model for wound healing in the intestinal tract that may have clinical relevance to mucosal repair in disorders of intestinal ulceration."

http://www.sciencemag.org/content/338/6103/51