Targeting the Bcl-2 family of proteins in Hodgkin lymphoma: in vitro cytotoxicity, target modulation and drug combination studies of the Bcl-2 homology 3 mimetic ABT-737

被引：19

作者：

Jayanthan, Aarthi ^{[1
,2
]}

Howard, Scott C. ^{[3
]}

Trippett, Tanya ^{[4
]}

Horton, Terzah ^{[5
]}

Whitlock, James A. ^{[6
]}

Daisley, Lara ^{[1
,2
]}

Lewis, Victor ^{[1
,2
]}

Narendran, Aru ^{[1
,2
]}

机构：

[1] Alberta Childrens Prov Gen Hosp, Div Pediat Oncol, Calgary, AB T3B 6A8, Canada

[2] Alberta Childrens Prov Gen Hosp, Hughes Childrens Canc Res Ctr, Calgary, AB T3B 6A8, Canada

[3] St Jude Childrens Hosp, Memphis, TN 38105 USA

[4] Mem Sloane Kettering Canc Ctr, New York, NY USA

[5] Baylor Coll Med, Houston, TX 77030 USA

[6] Vanderbilt Univ, Med Ctr, Nashville, TN USA

来源：

LEUKEMIA & LYMPHOMA | 2009年 / 50卷 / 07期

关键词：

Hodgkin lymphoma; ABT-737; Bcl-2; apoptosis; targeted therapeutics; ACUTE LYMPHOBLASTIC-LEUKEMIA; REED-STEMBERG CELLS; EPSTEIN-BARR-VIRUS; NF-KAPPA-B; MULTIPLE-MYELOMA; INHIBITOR ABT-737; APOPTOTIC PATHWAY; STERNBERG CELLS; EXPRESSION; PROLIFERATION;

D O I：

10.1080/10428190902943069

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

With currently available treatment, patients with refractory Hodgkin lymphoma (HL) or those who relapse multiple times have an extremely poor prognosis. Therefore, new agents and novel therapeutic approaches are urgently needed. Antiapoptotic proteins such as Bcl-2 and Bcl-x have been associated with the growth and survival of Hodgkin Reed-Sternberg cells and are potential therapeutic targets. ABT-737 is a small molecule that inhibits the Bcl-2 family of apoptosis regulators. In this study, we show the concentration-dependent and time-dependent cytotoxicity of ABT-737 against cell lines derived from patients with HL. A concurrent reduction in a number of intracellular cell growth and survival related molecules, such as Bcl-2, Bcl-xl, NF-kappa B and survivin was also seen. Drug combination studies using a panel of conventional and novel therapeutic agents show that ABT-737 potentiates the activity of agents that have inherent anti-lymphoma activity and provide support for the evaluation of ABT-737 in the clinical setting.

引用

页码：1174 / 1182

页数：9

共 53 条

[21] Aberrant NF-κB signaling in lymphoma:: mechanisms, consequences, and therapeutic implications [J].

Jost, Philipp J. ;

Ruland, Juergen .

BLOOD, 2007, 109 (07) :2700-2707

[22]

Kanavaros P, 2000, HISTOL HISTOPATHOL, V15, P445, DOI 10.14670/HH-15.445

[23] Activity of vincristine, L-ASP, and dexamethasone against acute lymphoblastic leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo [J].

Kang, Min H. ;

Kang, Yun Hee ;

Szymanska, Barbara ;

Wilczynska-Kalak, Urszula ;

Sheard, Michael A. ;

Harned, Theresa M. ;

Lock, Richard B. ;

Reynolds, C. Patrick .

BLOOD, 2007, 110 (06) :2057-2066

[24] Expression of Bcl-2 family members and presence of Epstein-Barr virus in the regulation of cell growth and death in classical Hodgkin's lymphoma [J].

Kim, LH ;

Nadarajah, VS ;

Peh, SC ;

Poppema, S .

HISTOPATHOLOGY, 2004, 44 (03) :257-267

[25] ABT-737, an inhibitor of Bcl-2 family proteins, is a potent inducer of apoptosis in multiple myeloma cells [J].

Kline, M. P. ;

Rajkumar, S. V. ;

Timm, M. M. ;

Kimlinger, T. K. ;

Haug, J. L. ;

Lust, J. A. ;

Greipp, P. R. ;

Kumar, S. .

LEUKEMIA, 2007, 21 (07) :1549-1560

[26] Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia [J].

Konopleva, Marina ;

Contractor, Rooha ;

Tsao, Twee ;

Samudio, Ismael ;

Ruvalo, Peter P. ;

Kitada, Shinichi ;

Deng, Xingming ;

Zhai, Dayong ;

Shi, Yue-Xi ;

Sneed, Thomas ;

Verhaegen, Monique ;

Soengas, Maria ;

Ruvolo, Vivian R. ;

McQueen, Teresa ;

Schober, Wendy D. ;

Watt, Julie C. ;

Jiffar, Tilahun ;

Ling, Xiaoyang ;

Marini, Frank C. ;

Harris, David ;

Dietrich, Martin ;

Estrov, Zeev ;

McCubrey, James ;

May, W. Stratford ;

Reed, John C. ;

Andreeff, Michael .

CANCER CELL, 2006, 10 (05) :375-388

[27] Apoptosis-based dual molecular targeting by INNO-406, a second-generation Bcr-Abl inhibitor, and ABT-737, an inhibitor of antiapoptotic Bcl-2 proteins, against Bcr-Abl-positive leukemia [J].

Kuroda, J. ;

Kimura, S. ;

Strasser, A. ;

Andreeff, M. ;

O'Reilly, L. A. ;

Ashihara, E. ;

Kamitsuji, Y. ;

Yokota, A. ;

Kawata, E. ;

Takeuchi, M. ;

Tanaka, R. ;

Tabe, Y. ;

Taniwaki, M. ;

Maekawa, T. .

CELL DEATH AND DIFFERENTIATION, 2007, 14 (09) :1667-1677

[28]

Kuroda J, 2006, P NATL ACAD SCI USA, V103, P14907, DOI 10.1073/pnas.0606176103

[29] Alteration of the mitochondrial apoptotic pathway is key to acquired paclitaxel resistance and can be reversed by ABT-737 [J].

Kutuk, Ozgur ;

Letai, Anthony .

CANCER RESEARCH, 2008, 68 (19) :7985-7994

[30] A new non-radioactive method for IL-2 bioassay [J].

Kwack, KB ;

Lynch, RG .

MOLECULES AND CELLS, 2000, 10 (05) :575-578

← 1 2 3 4 5 6 →