Bcl-2 antisense therapy in B-cell malignant proliferative disorders

被引：10

作者：

Chanan-Khan A. ^{[1
]}

Czuczman M.S. ^{[1
]}

机构：

[1] Department of Medicine, Lymphoma and Myeloma Section, Roswell Park Cancer Institute, Buffalo, NY 14263, Elm and Carlton Streets

来源：

Current Treatment Options in Oncology | 2004年 / 5卷 / 4期

关键词：

Multiple Myeloma; Chronic Lymphocytic Leukemia; Thalidomide; Bortezomib; Mantle Cell Lymphoma;

D O I：

10.1007/s11864-004-0017-3

中图分类号：

学科分类号：

摘要：

Overexpression of Bcl-2 oncogene has been clinically associated with an aggressive clinical course, chemotherapy and radiotherapy resistance, and poor survival in patients with malignant B-cell disorders. Patients with relapsed or refractory chronic lymphocytic leukemia, multiple myeloma, or non-Hodgkin's lymphoma have limited therapeutic options. Preclinical and early clinical data have shown that Bcl-2 oncoprotein can be decreased by Bcl-2 antisense therapy. Also, downregulation of Bcl-2 protein can result in reversal of chemotherapy resistance and improved antitumor activity of biologic agents. Various clinical trials are evaluating the role of targeting Bcl-2 as a mechanism to enhance the antitumor potential of chemotherapy and immunotherapy. Early results from these clinical studies are encouraging and confirm the proof of principle for antisense therapy. As current data mature, these trials will hopefully validate preliminary results and establish Bcl-2 antisense as an important addition to the current armamentarium used in the treatment of patients with B-cell neoplasms. Copyright © 2004 by Current Science Inc.

引用

页码：261 / 267

页数：6

共 30 条

[1]

Reed J.C., Bcl-2 family proteins: Regulators of apoptosis and chemoresistance in hematologic malignancies, Semin. Hematol., 34, SUPPL. 5, pp. 9-19, (1997)

[2]

Reed J.C., Bcl-2 family proteins, Oncogene, 17, pp. 3225-3236, (1998)

[3]

Tsujimoto Y., Gorham J., Cossman J., Et al., The t(14

[4]

18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining, Science, 229, pp. 1390-1393, (1985)

[5]

Wang H.G., Reed J.C., Mechanisms of Bcl-2 protein function, Histol. Histopathol., 13, pp. 521-530, (1998)

[6]

Lai R., Arber D.A., Chang K.L., Et al., Frequency of bcl-2 expression in non-Hodgkin's lymphoma: A study of 778 cases with comparison of marginal zone lymphoma and monocytoid B-cell hyperplasia, Mod. Pathol., 11, pp. 864-869, (1998)

[7]

Gascoyne R.D., Adomat S.A., Krajewski S., Et al., Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma, Blood, 90, pp. 244-251, (1997)

[8]

Milner A.E., Grand R.J., Vaughan A.T., Et al., Differential effects of Bcl-2 on survival and proliferation of human B-lymphoma cells following gamma-irradiation, Oncogene, 15, pp. 1815-1822, (1997)

[9]

Logsdon M.D., Meyn Jr. R.E., Besa P.C., Et al., Apoptosis and the Bcl-2 gene family: Patterns of expression and prognostic value in stage I and II follicular center lymphoma, Int. J. Radiat. Oncol. Biol. Phys., 44, pp. 19-29, (1999)

[10]

Martinka M., Comeau T., Foyle A., Et al., Prognostic significance of t(14

← 1 2 3 →