Blood, 15 June 2001, Vol. 97, No. 12, pp. 3902-3909
NEOPLASIA
MCL1 transgenic mice exhibit a high incidence of
B-cell lymphoma manifested as a spectrum of histologic
subtypes
Ping Zhou,
Norman B. Levy,
Haiyi Xie,
Liping Qian,
Chi-Yu Gregory Lee,
Randy D. Gascoyne, and
Ruth W. Craig
From the Departments of Pharmacology and Toxicology,
Pathology, and Community and Family Medicine, Dartmouth Medical School,
Hanover, NH; and Andrology Laboratory, Department of Obstetrics and
Gynecology, University of British Columbia; and Vancouver Cancer
Center, British Columbia Cancer Agency, Vancouver, BC, Canada.
Viability-promoting genes such as BCL2 play an
important role in human cancer but do not directly cause aggressive
tumors. BCL2 transgenic mice develop lymphoma at low
frequency, hindering studies of tumorigenesis and its inhibition in the
presence of such gene products. MCL1 is a member of the
BCL2 family that is highly regulated endogenously and that
promotes cell viability and immortalization when introduced
exogenously. Mice expressing an MCL1 transgene in
hematolymphoid tissues have now been monitored for an extended period
and were found to develop lymphoma with long latency and at high
probability (more than 85% over 2 years). In most cases, the disease
was widely disseminated and of clonal B-cell origin. A variety of
histologic subtypes were seen, prominently follicular lymphoma and
diffuse large-cell lymphoma. MCL1 thus sets the stage for
the development of lymphoma as does BCL2, disease occurring
with high probability and recapitulating a spectrum of subtypes as seen
in human patients. These findings with the transgene underscore the
importance of the normal, highly regulated pattern of MCL1
expression, in addition to providing a model for studying tumorigenesis
and its inhibition in the presence of a viability promoting
BCL2 family member.
