Lymphoma is a cancer of the immune system. White blood cells divide again and again, spreading abnormally throughout the body. Lymphomas can arise from two types of white blood cells, T cells or B cells, which divide uncontrollably when the molecular mechanisms that keep them in check go awry. A new study led by Dr. Robert Rickert, professor and director of Sanford-Burnham’s Inflammatory Diseases Program, explores the roles of two enzymes, called SHIP and PTEN, in B cell growth and proliferation.
“PTEN usually gets all the attention,” Dr. Rickert explained. “But here we show for the first time that SHIP is also a major tumor suppressor in B cells.”
The results, published this week in The Journal of Experimental Medicine, show that SHIP and PTEN act cooperatively to suppress B cell lymphoma. This new information could impact several anti-lymphoma therapies currently in development.
PTEN and SHIP suppress tumors by keeping a damper on PI3K, an enzyme that promotes cellular growth, survival and proliferation. PI3K signaling is altered in a number of different cancers. If PTEN is missing in T cells, the damper is removed, cells grow out of control and T cell lymphomas result. Surprisingly, this study showed that B cells deficient in either PTEN or SHIP are fine. But if mouse B cells are engineered to lack both PTEN and SHIP, lethal B cell abnormalities develop.
In addition to increasing our understanding of B cell biology, this research has implications for lymphoma treatments currently in development. One such treatment targets drug-resistant B cells by depleting the body of B cell activating factor (BAFF), a compound that promotes their survival. In this new model, however, Dr. Rickert and colleagues found that B lymphoma cells still proliferate without BAFF.
On a more positive note, this study supports the development of anti-lymphoma drugs that mimic PTEN and SHIP activity by inhibiting PI3K. “Several companies are making PI3K inhibitors to treat certain kinds of lymphomas,” Dr. Rickert said. “I think this system could provide a useful new preclinical model to study PI3K-dependent B cell malignancies.”