A team at the University of California Los Angeles, led by Dr Michael Teitell, and collaborators at Harvard Medical School, The Rockefeller University and the National Institutes of Health have been studying this gene and its role in the development of B-cell non-Hodgkin lymphoma (B-NHL), and will publish their findings in the journal Blood.
Using cancer cell samples from lymphoma patients, the researchers discovered that abnormal TCL1 expression is a frequent abnormality in B-NHL. The researchers then engineered mice to aberrantly express the TCL1 gene and those mice developed B-NHLs at a very high rate, within the germinal centers of lymphoid tissues, such as lymph nodes and the spleen, where B cells normally develop.
Further, the researchers determined that these lymphomas only arise when the TCL1 abnormalities are accompanied by companion genetic defects. The researchers identified several of these, including the Myc oncogene, already known to play a role in causing lymphoma.
This finding is consistent with current understanding that cancer usually involves defects in more than one critical gene, including defects that activate cancer-causing genes (oncogenes) like TCL1 and defects that inactivate cancer-preventing genes (tumor suppressors).
The researchers will next determine which molecular defects that occur in mouse lymphomas also occur in human lymphomas. The researchers anticipate that one or more newly identified molecules will emerge as valid targets for safe and effective targeted therapies for NHL patients.
The information can also be used to design improved tests for the diagnosis and classification of NHLs so that patients can receive the best possible individualized treatment.
“We are hopeful that these findings will lead to the further development of targeted therapies for certain NHL patients while producing fewer side effects than standard therapies,” Dr Teitell said.