The role of TRAIL death receptors in the treatment of hematological malignancies

被引：38

作者：

Henson, Elizabeth S. ^{[1
,2
]}

Johnston, James B. ^{[1
,3
]}

Gibson, Spencer B. ^{[1
,2
]}

机构：

[1] Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada

[2] Univ Manitoba, Dept Biochem & Med Genet, Winnipeg, MB R3E 0V9, Canada

[3] Univ Manitoba, Dept Internal Med, Winnipeg, MB R3E 0V9, Canada

来源：

LEUKEMIA & LYMPHOMA | 2008年 / 49卷 / 01期

关键词：

TRAIL; TRAIL receptors; transcription; apoptosis; therapy;

D O I：

10.1080/10428190701713655

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising new treatment for the hematological malignancies. TRAIL induces apoptosis by binding to its two death receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2). The extent of apoptosis by TRAIL is tightly regulated by the expression of these receptors and by downstream signaling. Chemotherapeutic agents increase the expressions of DR4 and DR5 on tumor cells through the activation of various transcription factors and there is enhanced killing on combining these agents with TRAIL. In this review, we will discuss the mechanism of TRAIL death receptor-induced apoptosis and the regulation of DR4 and DR5 expression. In particular, we will focus on the regulation of TRAIL death receptor signaling in hematological malignancies and the mechanisms responsible for the sensitization of leukemia and lymphoma cells to TRAIL-induced apoptosis by chemotherapy. Finally, we shall review the clinical data regarding the use of recombinant TRAIL and activating monoclonal antibodies against the TRAIL death receptors in the hematological malignancies.

引用

页码：27 / 35

页数：9

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