Diffuse large B cell lymphomaDiffuse large B cell lymphoma is the commonest type of lymphoma in adults. Many patients can be cured with chemotherapy plus immunotherapy such as Rituximab (Mabthera) but some patients have worse outcomes.

2 ‘bad guy’ gene rearrangements: c-MYC and BCL-2

We have a growing understanding of some of the genetic ‘errors’ in DLBCL that define these poorer-prognosis patients. Two important examples are rearrangements of genes as they sit on the chromosome, called c-MYC and BCL-2. 10-30 percent of cases of DLBCL have these genetic abnormalities.

BET inhibitor drugs can suppress the activity of cancer-causing genes.

Medications that target these genetic abnormalities are being developed. One group of proteins in the body, called BET proteins (BET stands for bromodomain and extraterminal family of proteins) give c-MYC a leg-up and enable it to cause uncontrolled growth of cells, leading to lymphoma. New drugs called BET inhibitors can reduce the activity of c-MYC . Dr Sally Trabucco from the University of Massachusetts School of Medicine has developed one such drug, currently called JQ1.

In the laboratory, this drug suppresses c-MYC, stops lymphoma cells from growing, and even causes the lymphoma cells to die. In animal models of lymphoma it also significantly improves the survival of affected mice.

What does this mean for DLBCL therapy?

BET inhibitors are just one of many novel approaches to treating lymphoma. As scientists unravel the errors within a cell that cause cancer, these errors can then become the targets for new drug discovery. Although DLBCL is often a curable condition, the subgroup of patients with these high-risk genetic errors are a group with a high need of novel approaches. It is possible that by combining drugs like JQ1 with chemotherapy and immunotherapy, survival in these patients could be dramatically improved. The next step is clinical trials to deterimine if these drugs are safe in humans, and then trials to determine if adding these drugs to standard therapy achieves better outcomes.


Dr Kirsten Herbert Dec 2014

Ref: Trabucco SE et al. Inhibition of bromodomain proteins for the treatment of human diffuse large B-cell lymphoma. Clin Cancer Res 2014. Epub ahead of print.