BURKITT’S LYMPHOMA - A HUMAN TUMOR MODEL
Ian Magrath
International
Network for Cancer Treatment and Research, Brussels, Belgium
Burkitt’s
lymphoma (BL), since its identification as a clinico-pathological entity
some 40 years ago, has provided a model tumor for cancer epidemiology,
pathogenesis and treatment.
One of Burkitt’s major contributions was to demonstrate the climatic
limits to the distribution of the tumor in Africa. Since this coincided with the
distribution of virus vectored diseases, this led directly to the search
for a viral etiology, and to the discovery of Epstein-Barr virus (EBV)- now
recognized generally recognized as causally associated with a subset of
BL. EBV is also associated with
a number of other human neoplasms - an association which has implications
for both the prevention and treatment of these diseases. Ironically, it seems now that the
climatic distribution is not due to the EBV association, but to an
etiological co-factor, malaria. Subsequently, a non-random chromosomal
translocation which juxtaposes an oncogene, c-myc, to immunoglobulin genes, was
identified in BL, and this may also now be considered as a cardinal feature
of the disease. The myc-immunoglobulin
translocation provides not only an explanation for the deregulated growth
of BL cells, caused by inappropriate expression of c-myc, but also a
model which led to the identification of many other chromosomal
translocations in lymphoid neoplasia.
With respect to therapy, BL was one of the first tumors in which it
was demonstrated that cure could be achieved with chemotherapy alone - even
with a single drug - a source of considerable encouragement to pioneer
chemotherapists. Whilst cure
rates were initially quite modest (approximately 20%), with the advent of therapy
directed towards the CNS, these improved to approximately 40%, and upon
this foundation, cure rates of children with B cell lymphomas in other
world regions have now reached approximately 90%. Unfortunately, cure rates in Africa remain low. BL provides, perhaps, an additional
lesson - that tumors, may come in families - rather like proteins with
similar structural features but different functions. Defined at a histological level, BL
differs with respect to epidemiological (climatic dependence on distribution),
pathogenetic (EBV association), molecular (chromosome breakpoint locations)
and clinical features (e.g. the frequency of jaw tumors) in different world
regions, suggesting that BL is a set of closely related entities with
different proportions of each subtype in different world regions. It is not know whether this has
treatment implications. In
summary, this rare tumor,
literally put on the map in sub-Saharan Africa, has led to major advances
in the epidemiology, pathogenesis and treatment of a broad range of
cancers.