Bcl-2, Bcl-x, Bax, and Bak expression in short- and long-lived patients with diffuse large B-cell lymphomas

Osnat Bairey, Yael Zimra, Mati Shaklai, Elimelech Okon, Esther Rabizadeh

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64 Scopus citations

Abstract

Long-term cure is now possible for ~50% of all patients with aggressive non-Hodgkin's lymphoma (NHL). Apoptosis-related proteins play an important role in the chemosensitivity or chemoresistance of tumors. We examined the role of Bcl-2 family proteins in aggressive NHL. We retrospectively selected two groups of patients by clinical outcome: 24 patients with chemoresponsive disease and long survival (median, 88 months); and 20 patients with chemoresistant disease and short survival (median, 8 months). The expression of the apoptosis-regulating proteins, Bcl-2, Bcl-X, Bax, and Bak, in the initial biopsy samples was examined with immunohistochemical methods. Specimens containing >10% immunostained tumor cells were considered immunopositive. An inverse association was found between length of patient survival and expression of Bcl-2, Bcl-X, and Bax. Bcl-2 was expressed in 75% of short-lived patients but in only 42% of the long-lived ones (P = 0.026). Bcl-X expression was also higher in the short-lived patients (40% versus 12.5%; P = 0.036). Unexpectedly, Bax expression was strongly associated with short survival (60% versus 21%; P = 0.008). Several combinations of protein expression, i.e., Bcl-2 with Bax, Bcl-2 with Bcl-X, and Bcl-X with Bax, were different between the groups: a positive expression of these proteins was found in the short-lived patients. Furthermore, a strong association was found between the expression of Bcl-2 and Bcl-X, suggesting that BcI-X potentiates rather than replaces the effect of Bcl-2 in NHL. In diffuse large B-cell NHL, Bcl-2, Bcl-X, and Bax expression alone or in combination is associated with chemoresistance and short-term survival.

Original languageEnglish
Pages (from-to)2860-2866
Number of pages7
JournalClinical Cancer Research
Volume5
Issue number10
StatePublished - Oct 1999
Externally publishedYes

Bibliographical note

Funding Information:
ACKNOWLEDGMENT The views expressed in this report are those of the authors and do not reflect the official position of the United States Air Force, Department of Defense, or U.S. Government. FUNDING INFORMATION This work, including the efforts of Alex Li, was partially funded by DOD |Defense Threat Reduction Agency (DTRA).

Funding Information:
This work, including the efforts of Alex Li, was partially funded by DOD | Defense Threat Reduction Agency (DTRA).

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