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Unbalanced Expression of Bcl-2 Family Proteins in
Follicular Lymphoma: Contribution of CD40 Signaling in Promoting
Survival
Paolo Ghia,
Vassiliki A. Boussiotis,
Joachim L. Schultze,
Angelo
A. Cardoso,
David M. Dorfman,
John G. Gribben,
Arnold S. Freedman, and
Lee M. Nadler
From the Department of Adult Oncology, Dana-Farber Cancer Institute;
the Departments of Medicine and Pathology, Brigham and Women's
Hospital; and Harvard Medical School, Boston, MA.
Although highly responsive, advanced stage follicular lymphoma (FL)
is not curable with conventional treatment. This relative resistance is
thought to be due to the t(14;18) that results in the constitutive
overexpression of the death-inhibiting protein bcl-2. However, the
observation that FL cells are sensitive to treatment in vivo and prone
to apoptosis on in vitro culture questions whether bcl-2 alone is
responsible for the pathogenesis and clinical behavior of this disease.
Therefore, multiple genes are likely to be involved in both the
lymphomagenesis and the clinical course of FL. We examined whether
expression of other bcl-2 family genes might also be operative. Here,
we show that FL cells display a different pattern of expression of
bcl-2 family proteins from normal germinal center (GC) B cells that are
thought to be their normal counterpart. FL cells express the
death-suppressor proteins bcl-2, bcl-xL, and mcl-1; whereas
GC B cells express bcl-xL and mcl-1 but also the
proapoptotic proteins bax- and bad. Although maintaining
constitutive levels of bcl-2 and mcl-1, FL cells are not protected from
apoptosis when cultured in vitro. Their propensity to undergo apoptosis
is temporally associated with downregulation of bcl-xL.
More importantly, activation of FL cells via CD40 not only prevents
downregulation but increases the level of bcl-xL expression
and results in promotion of survival. These results support the
hypothesis that the overexpression of bcl-2 is not the only
antiapoptotic mechanism responsible for the pathogenesis of FL.
Survival of FL cells is determined by a number of death-inhibiting proteins, among which bcl-xL appears to have the most
critical role. Moreover, these findings are consistent with the
hypothesis that, although FL cells are malignant, they respond to
microenvironmental signals such as CD40L that appear to contribute to
their survival through the upregulation of death-inhibiting proteins.
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 244-251
© 1998 by The American Society of Hematology.
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|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
|
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628 - 635.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
R. C.T. Aguiar, Y. Yakushijin, S. Kharbanda, S. Tiwari, G. J. Freeman, and M. A. Shipp
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October 1, 1999;
94(7):
2403 - 2413.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. G. Wickremasinghe and A. V. Hoffbrand
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June 1, 1999;
93(11):
3587 - 3600.
[Full Text]
[PDF]
|
|
|
|
|
|
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November 1, 1998;
92(9):
3381 - 3387.
[Abstract]
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