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Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 1013-1020
From the Department of Biochemistry, Boston University School of
Medicine, Boston, MA; Department of Immunology and Cell Biology,
Istituto di Ricerche Farmacologiche `Mario Negri,' Milano, Italy.
A-myb is a member of the myb family of transcription
factors, which regulates proliferation, differentiation, and apoptosis of hematopoietic cells. A-Myb expression is normally
restricted to the proliferating B-cell centroblasts and transgenic mice
overexpressing A-myb displayed enhanced hyperplasia of the
lymph nodes. Because A-Myb is highly expressed in several subtypes of
human B-cell neoplasias, we sought to determine whether the
A-myb gene promoted proliferation and survival of B
lymphocytes, using the WEHI 231 and CH33 murine B-cell lymphomas
as models. Here, we show that ectopic expression of A-myb
rescues WEHI 231 and CH33 cells from growth arrest and apoptosis
induced by anti-IgM treatment. Previously, we demonstrated an essential
role of the c-myc gene in promoting cell survival of WEHI 231 cells in response to a variety of apoptotic stimuli. Furthermore, we
and others have shown that the c-myc gene is potently
transactivated by A-Myb in several cell types. Thus, we sought to
determine whether c-Myc would mediate the A-Myb antiapoptotic effect in
B cells. Here we show that ectopic expression of
A-myb leads to maintenance of c-myc expression, and
that expression of antisense c-myc RNA ablates A-Myb-mediated
survival signals. Thus, these findings strongly implicate the
A-myb gene in the regulation of B-cell survival and confirm the
c-myc gene as one of the downstream targets of A-myb in
these cells. Overall, our observation suggests that A-myb
expression may be relevant to the pathology of human B-cell neoplasias.
This article has been cited by other articles:
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| Copyright © 2000 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
