Previous attempts to engineer such "Burkitt's mice" failed, but a team of
scientists at the National Institutes of Health (NIH) finally came up with
the right genetic mix. "We in effect created a 'mini-gene' that reproduces
the cancer as it occurs in people," says Herbert C. Morse III, M.D., chief
of the immunopathology lab at the National Institute of Allergy and
Infectious Diseases (NIAID). The results of this work, supported by NIAID
and the National Cancer Institute (NCI), are detailed in the current issue
of the Journal of Experimental Medicine.
"This new animal model may allow researchers to find ways to treat Burkitt's
patients who don't respond to the standard treatment," says Dr. Morse. "It
will also help us understand why the cells 'go bad' to cause this
malignancy." Scientists still don't know all the factors that contribute to
Burkitt's lymphoma in people, despite having created Burkitt's mice.
Scientists do know that Burkitt's lymphoma arises in the immune system, and
that the groundwork for the cancer is laid when a gene called MYC
(pronounced "mick") is accidentally moved from its usual spot on chromosome
8 to a new location, often on chromosome 14. Normally, the MYC gene, which
stimulates cell growth, is strictly controlled by nearby regulator genes on
chromosome 8. But when MYC slips away to a different chromosome, it also
evades its controls. Under the looser supervision of regulatory genes that
govern the immune system, MYC "goes ripping out of control," Dr. Morse
explains, causing runaway growth of the immune system's B cells, which in
turn leads to tumors called lymphomas.
But scientists have much more to learn about how other genetic mutations,
environmental factors and infectious agents, such as the Epstein-Barr virus,
work together to cause Burkitt's lymphoma. In fact, studying the Burkitt's
mice may lead to new understandings about why some people are predisposed to
Burkitt's lymphoma, while other people are predisposed to other kinds of
cancers, says Siegfried Janz, M.D., of NCI. "The only way to find this out
is to invest basic research into mouse models of cancer," he argues.
Clinicians might also use such a mouse model to test new treatments, he
Achieving a Burkitt's mouse would not have been possible without previous
work done by other NIAID scientists, Morse notes, particularly Janet
Hartley, Ph.D., and Torgny Frederickson, Ph.D., who have spent years
examining lymphomas in mice. The success also owes much to collaborator
George Bornkamm, M.D., and his team at the Institute for Clinical Molecular
Biology and Tumor Genetics in Munich, Germany.
Burkitt's lymphoma was first identified in 1958 by Denis Parsons Burkitt, an
English surgeon in Africa who noticed it among the children there. The
disease accounts for over half of all childhood cancers in Africa, where it
affects about two out of 100,000 children every year. Incidence in Western
countries is much lower, but has been on the rise with the spread of AIDS,
since the cancer also strikes adults with compromised immune systems.
NIAID is a component of the NIH. NIAID supports basic and applied research
to prevent, diagnose, and treat infectious and immune-mediated illnesses,
including HIV/AIDS and other sexually transmitted diseases, tuberculosis,
malaria, autoimmune disorders, asthma and allergies.
Press releases, fact sheets and other NIAID-related materials are available
on the NIAID Web site at http://www.niaid.nih.gov.