The genes TEL2 and MYC cooperate with each other to promote pediatric cases of the immune system cancer B-cell lymphoma. This finding, from investigators at St. Jude Children's Research Hospital, is published in the current issue of Molecular Cell Biology (MCB).
B-cell lymphoma is a cancer in which the antibody-producing cells (B lymphocytes) multiply uncontrollably and crowd out other blood cells. The St. Jude researchers report that TEL2 cooperates with MYC to increase the chance that a certain mutation will occur in precancerous B lymphocytes, permitting these cells to become cancerous. This mutation inactivates the function of p53, a gene that orchestrates the ability of abnormal lymphocytes to commit suicide--ridding the body of potentially cancerous cells.
"The study's findings strongly suggest that physicians should look for TEL2 activity in a patient's B-cells as part of the diagnosis of B-cell lymphoma," said Gerard Grosveld, Ph.D., chair of St. Jude Genetics and Tumor Cell Biology. "TEL2 should also be considered a potential target for novel drugs to treat this disease." Grosveld is senior author of the MCB report.
The TEL2 gene is part of a family of genes called ETS transcription factors. Transcription factors prompt the cell to read the code of a specific gene and produce copies of RNA. RNA then directs the production of the protein that the gene codes for. The gene TEL1, which works to slow cell growth and multiplication, is another member of the ETS family and is a known target of mutations in human leukemia. Grosveld's group previously identified TEL2 and noted its similarity to TEL1, which prompted them to investigate whether TEL2 also played a role in leukemia. In the MCB study, the investigators discovered that, unlike TEL1, TEL2 promotes cell multiplication, playing an indirect role in the development of B lymphoma.
"TEL2 doesn't directly cause cancer," Grosveld said. "Instead, this gene promotes the development of lymphoma by enlarging the B lymphocyte population. This increases the likelihood that at least a few of the cells acquire a mutation eliminating p53 function just by chance. In the absence of p53, the cells remains alive and become cancerous."
The study's findings help explain the interlocking roles of MYC, TEL2, and p53 in the development of B lymphoma. It was already known that many human B-cell lymphomas over-express the MYC gene, either because the tumor cells acquire additional copies of this gene or because the cells suffer mutations that affect control over the level of MYC expression. Excess MYC expression spurs the cells to proliferate. This abnormal behavior then triggers p53 to instruct these overzealous cells to undergo apoptosis.