Breaking therapy resistance of follicular lymphoma

A lot of therapies but no cures exist for follicular lymphoma (FL), which is the second most common type of non-hodgkin’s lymphoma. A Swiss-Canadian research team led by Elisa Oricchio from EFPL in Lausanne has now identified the driver mutation, which prevents response to targeted therapies. Within the 6q region of chromosome No. VI, which is missing in 25-30% of follicular lymphoma cases, the researchers screened 81 genes for for their ability to promote uncontrolled cell growth in culture and uncovered SESTRIN1 as a potential tumour suppressor.

Knocking down the SESTRIN1 gene in mouse models accelerated FL development. Tumours lacking SESTRIN1 also did not respond to an experimental targeted therapy for follicular lymphoma called GSK126. In addition, Oricchio and colleagues discovered that GSK126’s target, the histone methyl transferase EZH2, turns on SESTRIN1, to prevent tumour cells from making proteins.

Interestingly, some lymphomas have mutant forms of EZH2, which the scientists found can render those cancers sensitive to a new class of targeted therapies known as bifunctional mTOR inhibitors. According to the authors, efforts to develop lymphoma therapeutics should take into account how mutations in SESTRIN1 and EZH2 might influence the effectiveness of anticancer interventions.