New therapeutic target for B-cell lymphoma

A study led by researchers at the University of Massachusetts Medical School shows that a particular type of lymphoma ( diffuse large B-cell lymphoma, or DLBCL ) could be treated if normal aging program was activated in tumor cells. In this manner, tumor cells would not be able to divide and proliferate anymore. Researchers found that Smurf2 protein involved in senescence, or cellular aging, acts as a tumor suppressor in DLBCL . This new function of Smurf2 protein could be an important therapeutic target in the treatment of DLBCL, researchers believe.

Hong Zhang , PhD, assistant professor of Cell & Developmental Biology at UMMS and senior author of the study, said that normally this signaling pathway is responsible for the suppression of cell proliferation and senescence. He explained, however, that human DLBCL expresses low levels of Smurf2 protein which means that proliferation and cell division are uncontrolled. Thus restoring Smurf2 protein expression could provide therapeutic benefits for patients with DLBCL. Rachel Gerstein, PhD, Associate Professor of Microbiology and Physiological Systems at UMMS, and co-author of the study, pointed out that the mean age of diagnosis is about 60 years. Since this cancer occurs mostly in the elderly, it is interesting to look for the connection between this feature of lymphoma and cell aging.

Diffuse large B-cell lymphoma is a cancer of B cells, the immune cells responsible for producing antibodies. DLBCL is one of the most common forms of non-Hodgkin lymphoma in adults and it is estimated that in 2013 in the United States 70,000 people will be diagnosed with non-Hodgkin lymphoma. Standard chemotherapy, called R-CHOP, consists of a combination therapy that includes a monoclonal antibody, a steroid and three other drugs ( rituximab , cyclophosphamide, doxorubicin, vincristine, and prednisone ). However, it seems that half of patients diagnosed with DLBCL do not respond to standard treatment.

Another study published in 2012 by Dr. Zhang has shown that mice that were deficient in Smurf2 protein spontaneously developed certain tumors, including B cell lymphoma. In order to find out the link between human DLBCL and Smurf2 protein, researchers analyzed the expression of this protein in patients with DLBCL. In this way they learned that an important subset of patients had a low expression of Smurf2; moreover, it appears that low levels of this protein was correlated with a worse prognosis.

Now a team of researchers at the Biomedical Sciences UMMS showed that Smurf2 is actually part of a complex signaling pathway involved in cell division and proliferation ( which includes transcriptional regulator YY1 and the regulatory genes c -Myc ). So, in DLBCL, the lack of Smurf2 leads to uncontrolled cell proliferation for cells. Now researchers want to find molecules that mimic the Smurf2 protein in order to suppress cell division in DLBCL .