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Citations to this article

Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737
Victoria Del Gaizo Moore, … , Carl D. Novina, Anthony Letai
Victoria Del Gaizo Moore, … , Carl D. Novina, Anthony Letai
Published January 2, 2007
Citation Information: J Clin Invest. 2007;117(1):112-121. https://doi.org/10.1172/JCI28281.
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Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737

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Abstract

Antiapoptotic B cell leukemia/lymphoma 2 (BCL2) family proteins are expressed in many cancers, but the circumstances under which these proteins are necessary for tumor maintenance are poorly understood. We exploited a novel functional assay that uses BCL2 homology domain 3 (BH3) peptides to predict dependence on antiapoptotic proteins, a strategy we call BH3 profiling. BH3 profiling accurately predicts sensitivity to BCL2 antagonist ABT-737 in primary chronic lymphocytic leukemia (CLL) cells. BH3 profiling also accurately distinguishes myeloid cell leukemia sequence 1 (MCL1) from BCL2 dependence in myeloma cell lines. We show that the special sensitivity of CLL cells to BCL2 antagonism arises from the requirement that BCL2 tonically sequester proapoptotic BIM in CLL. ABT-737 displaced BIM from BCL2’s BH3-binding pocket, allowing BIM to activate BAX, induce mitochondrial permeabilization, and rapidly commit the CLL cell to death. Our experiments demonstrate that BCL2 expression alone does not dictate sensitivity to ABT-737. Instead, BCL2 complexed to BIM is the critical target for ABT-737 in CLL. An important implication is that in cancer, BCL2 may not effectively buffer chemotherapy death signals if it is already sequestering proapoptotic BH3-only proteins. Indeed, activator BH3-only occupation of BCL2 may prime cancer cells for death, offering a potential explanation for the marked chemosensitivity of certain cancers that express abundant BCL2, such as CLL and follicular lymphoma.

Authors

Victoria Del Gaizo Moore, Jennifer R. Brown, Michael Certo, Tara M. Love, Carl D. Novina, Anthony Letai

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Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 Total
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Cell Death and Disease 2018
BH3-only proteins are dispensable for apoptosis induced by pharmacological inhibition of both MCL-1 and BCL-XL
G Greaves, M Milani, M Butterworth, RJ Carter, DP Byrne, PA Eyers, X Luo, GM Cohen, S Varadarajan
Cell Death and Differentiation 2018
BH3 Mimetic ABT-199 Enhances the Sensitivity of Gemcitabine in Pancreatic Cancer in vitro and in vivo
Y Zhou, H Liu, R Xue, W Tang, S Zhang
Digestive Diseases and Sciences 2018
Monitoring and Management of Toxicities of Novel B Cell Signaling Agents
J Rhodes, A Mato, JP Sharman
Current Oncology Reports 2018
BCL-2 inhibition in AML: an unexpected bonus?
M Konopleva, A Letai
Blood 2018
Statins enhance efficacy of venetoclax in blood cancers
JS Lee, A Roberts, D Juarez, TT Vo, S Bhatt, L Herzog, S Mallya, RJ Bellin, SK Agarwal, AH Salem, T Xu, J Jia, L Li, JR Hanna, MS Davids, AG Fleischman, S OBrien, LT Lam, JD Leverson, A Letai, JH Schatz, DA Fruman
Science Translational Medicine 2018
Anti-apoptotic A1 is not essential for lymphoma development in Eµ-Myc mice but helps sustain transplanted Eµ-Myc tumour cells
M Mensink, NS Anstee, M Robati, RL Schenk, MJ Herold, S Cory, CJ Vandenberg
Cell Death and Differentiation 2018
Targeting BCL-2 in Hematologic Malignancies
N Khan, B Kahl
Targeted Oncology 2018
Phosphorylation switches Bax from promoting to inhibiting apoptosis thereby increasing drug resistance
J Kale, O Kutuk, GC Brito, TS Andrews, B Leber, A Letai, DW Andrews
EMBO reports 2018
S55746 is a novel orally active BCL-2 selective and potent inhibitor that impairs hematological tumor growth
P Casara, J Davidson, A Claperon, GL Toumelin-Braizat, M Vogler, A Bruno, M Chanrion, G Lysiak-Auvity, TL Diguarher, JB Starck, I Chen, N Whitehead, C Graham, N Matassova, P Dokurno, C Pedder, Y Wang, S Qiu, AM Girard, E Schneider, F Gravé, A Studeny, G Guasconi, F Rocchetti, S Maïga, JM Henlin, F Colland, L Kraus-Berthier, SL Gouill, MJ Dyer, R Hubbard, M Wood, M Amiot, GM Cohen, JA Hickman, E Morris, J Murray, O Geneste
Oncotarget 2018
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor
HG Ozer, D El-Gamal, B Powell, ZA Hing, JS Blachly, B Harrington, S Mitchell, NR Grieselhuber, K Williams, TH Lai, L Alinari, RA Baiocchi, L Brinton, E Baskin, M Cannon, L Beaver, VM Goettl, DM Lucas, JA Woyach, D Sampath, AM Lehman, L Yu, J Zhang, Y Ma, Y Zhang, W Spevak, S Shi, P Severson, R Shellooe, H Carias, G Tsang, K Dong, T Ewing, A Marimuthu, C Tantoy, J Walters, L Sanftner, H Rezaei, M Nespi, B Matusow, G Habets, P Ibrahim, C Zhang, EA Mathé, G Bollag, JC Byrd, R Lapalombella
Cancer Discovery 2018
DNA demethylation marks in chronic lymphocytic leukemia: it is time to let the cat out of the bag
C Bagacean, M Zdrenghea, CL Dantec, A Tempescul, C Berthou, Y Renaudineau
Future Science OA 2018
High PGAM5 expression induces chemoresistance by enhancing Bcl-xL-mediated anti-apoptotic signaling and predicts poor prognosis in hepatocellular carcinoma patients
J Cheng, D Qian, X Ding, T Song, M Cai, D Xie, Y Wang, J Zhao, Z Liu, Z Wu, Q Pang, L Zhu, P Wang, X Hao, Z Yuan
Cell Death and Disease 2018
Impaired immune surveillance accelerates accumulation of senescent cells and aging
Y Ovadya, T Landsberger, H Leins, E Vadai, H Gal, A Biran, R Yosef, A Sagiv, A Agrawal, A Shapira, J Windheim, M Tsoory, R Schirmbeck, I Amit, H Geiger, V Krizhanovsky
Nature Communications 2018
A Novel MCL1 Inhibitor Combined with Venetoclax Rescues Venetoclax-Resistant Acute Myelogenous Leukemia
HE Ramsey, MA Fischer, T Lee, AE Gorska, MP Arrate, L Fuller, KL Boyd, SA Strickland, J Sensintaffar, LJ Hogdal, GD Ayers, ET Olejniczak, SW Fesik, MR Savona
Cancer Discovery 2018
Bcl-w significantly contributes to B cell survival and lymphomagenesis
Clare Adams, Annette Kim, Ramkrishna Mitra, John Choi, Jerald Gong, Christine Eischen
Journal of Clinical Investigation 2017
Chronic lymphocytic leukaemia
TJ Kipps, FK Stevenson, CJ Wu, CM Croce, G Packham, WG Wierda, S O'Brien, J Gribben, K Rai
Nature Reviews Disease Primers 2017
Targeted activation of the SHP-1/PP2A signaling axis elicits apoptosis of chronic lymphocytic leukemia cells
E Tibaldi, MA Pagano, F Frezzato, V Trimarco, M Facco, G Zagotto, G Ribaudo, V Pavan, L Bordin, A Visentin, F Zonta, G Semenzato, AM Brunati, L Trentin
Haematologica 2017
Bruton’s tyrosine kinase inhibition increases BCL-2 dependence and enhances sensitivity to venetoclax in chronic lymphocytic leukemia
J Deng, E Isik, SM Fernandes, JR Brown, A Letai, MS Davids
Leukemia 2017
Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci
PJ Law, A Sud, JS Mitchell, M Henrion, G Orlando, O Lenive, P Broderick, HE Speedy, DC Johnson, M Kaiser, N Weinhold, R Cooke, NJ Sunter, GH Jackson, G Summerfield, RJ Harris, AR Pettitt, DJ Allsup, J Carmichael, JR Bailey, G Pratt, T Rahman, C Pepper, C Fegan, EP von Strandmann, A Engert, A Försti, B Chen, MI da Filho, H Thomsen, P Hoffmann, MM Noethen, L Eisele, KH Jöckel, JM Allan, AJ Swerdlow, H Goldschmidt, D Catovsky, GJ Morgan, K Hemminki, RS Houlston
Scientific Reports 2017
The Development and Current Use of BCL-2 Inhibitors for the Treatment of Chronic Lymphocytic Leukemia
BL Lampson, MS Davids
Current Hematologic Malignancy Reports 2017
Pathways and mechanisms of venetoclax resistance
P Bose, V Gandhi, M Konopleva
Leukemia & Lymphoma 2017
Targeting BET proteins improves the therapeutic efficacy of BCL-2 inhibition in T-cell acute lymphoblastic leukemia
S Peirs, V Frismantas, F Matthijssens, WV Loocke, T Pieters, N Vandamme, B Lintermans, MP Dobay, G Berx, B Poppe, S Goossens, BC Bornhauser, JP Bourquin, PV Vlierberghe
Leukemia 2017
Pharmacotherapy of relapsed/refractory chronic lymphocytic leukemia
AA Zahr, P Bose, MJ Keating
Expert Opinion on Pharmacotherapy 2017
The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma
Y Tu, J He, H Liu, HC Lee, H Wang, J Ishizawa, JE Allen, M Andreeff, RZ Orlowski, RE Davis, J Yang
Neoplasia (New York, N.Y.) 2017
Complementary dynamic BH3 profiles predict co-operativity between the multi-kinase inhibitor TG02 and the BH3 mimetic ABT-199 in acute myeloid leukaemia cells
M Pallis, F Burrows, J Ryan, M Grundy, C Seedhouse, A Abdul-Aziz, J Montero, A Letai, N Russell
Oncotarget 2017
Why do BCL-2 inhibitors work and where should we use them in the clinic?
J Montero, A Letai
Cell Death and Differentiation 2017
Overcoming mutational complexity in acute myeloid leukemia by inhibition of critical pathways
Y Saito, Y Mochizuki, I Ogahara, T Watanabe, L Hogdal, S Takagi, K Sato, A Kaneko, H Kajita, N Uchida, T Fukami, LD Shultz, S Taniguchi, O Ohara, AG Letai, F Ishikawa
Science Translational Medicine 2017
Recent therapeutic advances in chronic lymphocytic leukemia
P Bose, V Gandhi
F1000Research 2017
The BCL-2 arbiters of apoptosis and their growing role as cancer targets
JM Adams, S Cory
Cell Death and Differentiation 2017
Bruton’s tyrosine kinase inhibitors: first and second generation agents for patients with Chronic Lymphocytic Leukemia (CLL)
PA Thompson, JA Burger
Expert Opinion on Investigational Drugs 2017
Found in Translation: How Preclinical Research Is Guiding the Clinical Development of the BCL2-Selective Inhibitor Venetoclax
JD Leverson, D Sampath, AJ Souers, SH Rosenberg, WJ Fairbrother, M Amiot, M Konopleva, A Letai
Cancer Discovery 2017
Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis
D Lagares, A Santos, PE Grasberger, F Liu, CK Probst, RA Rahimi, N Sakai, T Kuehl, J Ryan, P Bhola, J Montero, M Kapoor, M Baron, X Varelas, DJ Tschumperlin, A Letai, AM Tager
Science Translational Medicine 2017
Bioluminescence Imaging Enhances Analysis of Drug Responses in a Patient-Derived Xenograft Model of Pediatric ALL
L Jones, J Richmond, K Evans, H Carol, D Jing, RT Kurmasheva, CA Billups, PJ Houghton, MA Smith, RB Lock
Clinical cancer research 2017
Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling
SJ Cook, K Stuart, R Gilley, MJ Sale
The FEBS journal 2017
Functional precision cancer medicine—moving beyond pure genomics
A Letai
Nature Medicine 2017
Bcl-2 proteins and calcium signaling: complexity beneath the surface
T Vervliet, JB Parys, G Bultynck
Oncogene 2016
High-content screening identifies kinase inhibitors that overcome venetoclax resistance in activated CLL cells
S Oppermann, J Ylanko, Y Shi, S Hariharan, CC Oakes, PM Brauer, JC Zuniga-Pflucker, B Leber, DE Spaner, DW Andrews
Blood 2016
Select Bcl-2 antagonism restores chemotherapy sensitivity in high-risk neuroblastoma
R Tanos, D Karmali, S Nalluri, KC Goldsmith
BMC Cancer 2016
Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia
AW Roberts, MS Davids, JM Pagel, BS Kahl, SD Puvvada, JF Gerecitano, TJ Kipps, MA Anderson, JR Brown, L Gressick, S Wong, M Dunbar, M Zhu, MB Desai, E Cerri, SH Enschede, RA Humerickhouse, WG Wierda, JF Seymour
New England Journal of Medicine 2016
The BH3 mimetic drug ABT-737 induces apoptosis and acts synergistically with chemotherapeutic drugs in thyroid carcinoma cells
M Broecker-Preuss, N Becher-Boveleth, S Müller, K Mann
Cancer Cell International 2016
The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism
MA Anderson, J Deng, JF Seymour, C Tam, SY Kim, J Fein, L Yu, JR Brown, D Westerman, EG Si, IJ Majewski, D Segal, SL Enschede, DC Huang, MS Davids, A Letai, AW Roberts
Blood 2016
BH3 profiling and a toolkit of BH3-mimetic drugs predict anti-apoptotic dependence of cancer cells
M Butterworth, A Pettitt, S Varadarajan, GM Cohen
British Journal of Cancer 2016
BIM mediates synergistic killing of B-cell acute lymphoblastic leukemia cells by BCL-2 and MEK inhibitors
K Korfi, M Smith, J Swan, TC Somervaille, N Dhomen, R Marais
Cell Death and Disease 2016
A fate worse than death: apoptosis as an oncogenic process
G Ichim, SW Tait
Nature Reviews Cancer 2016
Comparison of in vitro antileukemic activity of obatoclax and ABT-737
M Opydo-Chanek, L Mazur
Tumor Biology 2016
Chronic Lymphocytic Leukemia: Exploiting Vulnerabilities with Targeted Agents
J Maly, JS Blachly
Current Hematologic Malignancy Reports 2016
Directly targeting the mitochondrial pathway of apoptosis for cancer therapy using BH3 mimetics - recent successes, current challenges and future promise
KA Sarosiek, A Letai
FEBS Journal 2016
BCL2 Inhibitors as Anticancer Drugs: A Plethora of Misleading BH3 Mimetics
RS Soderquist, A Eastman
Molecular cancer therapeutics 2016
Microtubule destabilising agents: far more than just antimitotic anticancer drugs: MDA mechanisms of action
D Bates, A Eastman
British Journal of Clinical Pharmacology 2016
Duvelisib treatment is associated with altered expression of apoptotic regulators that helps in sensitization of chronic lymphocytic leukemia cells to venetoclax (ABT-199)
VM Patel, K Balakrishnan, M Douglas, T Tibbitts, EY Xu, JL Kutok, M Ayers, A Sarkar, R Guerrieri, WG Wierda, S O'Brien, N Jain, HM Stern, V Gandhi
Leukemia 2016
Targeting BCL2 With BH3 Mimetics: Basic Science and Clinical Application of Venetoclax in Chronic Lymphocytic Leukemia and Related B Cell Malignancies: Basic science and clinical application of venetoclax
AW Roberts, DC Huang
Clinical Pharmacology & Therapeutics 2016
Pharmacokinetic and pharmacodynamic evaluation of ibrutinib for the treatment of chronic lymphocytic leukemia: rationale for lower doses
P Bose, VV Gandhi, MJ Keating
Expert Opinion on Drug Metabolism & Toxicology 2016
Mitochondrial apoptosis and BH3 mimetics
H Dai, XW Meng, SH Kaufmann
F1000Research 2016
Acquired resistance to venetoclax (ABT-199) in t(14;18) positive lymphoma cells
J Bodo, X Zhao, L Durkin, AJ Souers, DC Phillips, MR Smith, ED Hsi
Oncotarget 2016
Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia
M Konopleva, DA Pollyea, J Potluri, B Chyla, L Hogdal, T Busman, E McKeegan, AH Salem, M Zhu, JL Ricker, W Blum, CD DiNardo, T Kadia, M Dunbar, R Kirby, N Falotico, J Leverson, R Humerickhouse, M Mabry, R Stone, H Kantarjian, A Letai
Cancer Discovery 2016
Defining specificity and on-target activity of BH3-mimetics using engineered B-ALL cell lines
Koss B, Ryan J, Budhraja A, Szarama K, Yang X, Bathina M, Cardone MH, Nikolovska-Coleska Z, Letai A, Opferman JT
Oncotarget 2016
SLAMF1/CD150 regulates chemotaxis, autophagy and therapy responses in chronic lymphocytic leukemia patients
Cinzia Bologna, Roberta Buonincontri, Sara Serra, Tiziana Vaisitti, Valentina Audrito, Davide Brusa, Andrea Pagnani, Marta Coscia, Giovanni D'Arena, Elisabetta Mereu, Roberto Piva, Richard Furman, Davide Rossi, Gianluca Gaidano, Cox Terhorst, Silvia Deaglio
Journal of Clinical Investigation 2015
miR-377-dependent BCL-xL regulation drives chemotherapeutic resistance in B-cell lymphoid malignancies
S Al-harbi, GS Choudhary, JS Ebron, BT Hill, N Vivekanathan, AH Ting, T Radivoyevitch, MR Smith, GC Shukla, A Almasan
Molecular Cancer 2015
Emerging understanding of Bcl-2 biology: Implications for neoplastic progression and treatment
C Correia, SH Lee, XW Meng, ND Vincelette, KL Knorr, H Ding, GS Nowakowski, H Dai, SH Kaufmann
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2015
The BCL2 Family: Key Mediators of the Apoptotic Response to Targeted Anticancer Therapeutics
AN Hata, JA Engelman, AC Faber
Cancer Discovery 2015
Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells
S Bruno, B Ledda, C Tenca, S Ravera, AM Orengo, AN Mazzarello, E Pesenti, S Casciaro, O Racchi, F Ghiotto, C Marini, G Sambuceti, A DeCensi, F Fais
Oncotarget 2015
Regulation of Bim in Health and Disease
RV Sionov, SA Vlahopoulos, Z Granot
Oncotarget 2015
How cell death shapes cancer
V Labi, M Erlacher
Cell Death and Disease 2015
The Evolving Role of Hematopoietic Cell Transplantation in Chronic Lymphocytic Leukemia
MS Davids, EP Alyea
Current Hematologic Malignancy Reports 2015
Potent and Specific Peptide Inhibitors of Human Pro-Survival Protein Bcl-xL
S Dutta, J Ryan, TS Chen, C Kougentakis, A Letai, AE Keating
Journal of Molecular Biology 2015
Mitochondrial Shape Governs BAX-Induced Membrane Permeabilization and Apoptosis
TT Renault, KV Floros, R Elkholi, KA Corrigan, Y Kushnareva, SY Wieder, C Lindtner, MN Serasinghe, JJ Asciolla, C Buettner, DD Newmeyer, JE Chipuk
Molecular Cell 2015
Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer
AC Faber, AF Farago, C Costa, A Dastur, M Gomez-Caraballo, R Robbins, BL Wagner, WM Rideout, CT Jakubik, J Ham, EJ Edelman, H Ebi, AT Yeo, AN Hata, Y Song, NU Patel, RJ March, AT Tam, RJ Milano, JL Boisvert, MA Hicks, S Elmiligy, SE Malstrom, MN Rivera, H Harada, BE Windle, S Ramaswamy, CH Benes, T Jacks, JA Engelman
Proceedings of the National Academy of Sciences 2015
A phase 2 study of the BH3 mimetic BCL2 inhibitor navitoclax (ABT-263) with or without rituximab, in previously untreated B-cell chronic lymphocytic leukemia
TJ Kipps, H Eradat, S Grosicki, J Catalano, W Cosolo, I Dyagil, S Yalamanchili, A Chai, S Saharanaman, E Punnoose, D Hurst, H Pylypenko
Leukemia & Lymphoma 2015
Combining Paclitaxel with ABT-263 Has a Synergistic Effect on Paclitaxel Resistant Prostate Cancer Cells
C Wang, SB Huang, MC Yang, YT Lin, IH Chu, YN Shen, YH Chiu, SH Hung, L Kang, YR Hong, CH Chen, A Villunger
PloS one 2015
BH3 Inhibitor Sensitivity and Bcl-2 Dependence in Primary Acute Lymphoblastic Leukemia Cells
SE Alford, A Kothari, FC Loeff, JM Eichhorn, N Sakurikar, HM Goselink, RL Saylors, I Jedema, JH Falkenburg, TC Chambers
Cancer research 2015
BCL2 Inhibitor (ABT-737): A Restorer of Prednisolone Sensitivity in Early T-Cell Precursor-Acute Lymphoblastic Leukemia with High MEF2C Expression?
S Kawashima-Goto, T Imamura, C Tomoyasu, M Yano, H Yoshida, A Fujiki, S Tamura, S Osone, H Ishida, A Morimoto, H Kuroda, H Hosoi, F Bertolini
PloS one 2015
Pharmacological and Protein Profiling Suggests Venetoclax (ABT-199) as Optimal Partner with Ibrutinib in Chronic Lymphocytic Leukemia
F Cervantes-Gomez, B Lamothe, JA Woyach, WG Wierda, MJ Keating, K Balakrishnan, V Gandhi
Clinical cancer research 2015
A seven-gene expression panel distinguishing clonal expansions of pre-leukemic and chronic lymphocytic leukemia B cells from normal B lymphocytes
BA McCarthy, S Yancopoulos, M Tipping, X Yan, XP Wang, F Bennett, W Li, M Lesser, S Paul, E Boyle, C Moreno, R Catera, BT Messmer, G Cutrona, M Ferrarini, JE Kolitz, SL Allen, KR Rai, AC Rawstron, N Chiorazzi
Immunologic Research 2015
Dexamethasone treatment promotes Bcl-2 dependence in multiple myeloma resulting in sensitivity to venetoclax
SM Matulis, VA Gupta, AK Nooka, HV Hollen, JL Kaufman, S Lonial, LH Boise
Leukemia 2015
BCL-2 Antagonism to Target the Intrinsic Mitochondrial Pathway of Apoptosis
CJ Gibson, MS Davids
Clinical cancer research 2015
Clinical significance of bax/bcl-2 ratio in chronic lymphocytic leukemia
MI Principe, MD Bo, T Bittolo, F Buccisano, FM Rossi, A Zucchetto, D Rossi, R Bomben, L Maurillo, M Cefalo, GD Santis, A Venditti, G Gaidano, S Amadori, P Fabritiis, V Gattei, GD Poeta
Haematologica 2015
A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2
AR Lavik, F Zhong, MJ Chang, E Greenberg, Y Choudhary, MR Smith, KS McColl, J Pink, FJ Reu, S Matsuyama, CW Distelhorst
Oncotarget 2015
Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue
T Lampl, JA Crum, TA Davis, C Milligan, VD Moore
Journal of visualized experiments : JoVE 2015
Knockdown of Peripheral Myelin Protein 22 Inhibits the Progression of Chronic Myeloid Leukemia
H Liu, H Cao, J Ta, W Zhang, Y Liu
Oncology research 2015
Co-targeting of Bcl-2 and mTOR pathway triggers synergistic apoptosis in BH3 mimetics resistant acute lymphoblastic leukemia.
Iacovelli S, Ricciardi MR, Allegretti M, Mirabilii S, Licchetta R, Bergamo P, Rinaldo C, Zeuner A, Foà R, Milella M, McCubrey JA, Martelli AM, Tafuri A
Oncotarget 2015
RPPA-based protein profiling reveals eIF4G overexpression and 4E-BP1 serine 65 phosphorylation as molecular events that correspond with a pro-survival phenotype in chronic lymphocytic leukemia
Shull AY, Noonepalle SK, Awan FT, Liu J, Pei L, Bollag RJ, Salman H, Ding Z, Shi H
Oncotarget 2015
Targeting ERK1/2-bim signaling cascades by BH3-mimetic ABT-737 as an alternative therapeutic strategy for oral cancer
Shin JA, Kim LH, Lee SJ, Jeong JH, Jung JY, Lee HN, Hong IS, Cho SD
Oncotarget 2015
The outcome of B-cell receptor signaling in chronic lymphocytic leukemia: proliferation or anergy
G Packham, S Krysov, A Allen, N Savelyeva, AJ Steele, F Forconi, FK Stevenson
Haematologica 2014
Both leukaemic and normal peripheral B lymphoid cells are highly sensitive to the selective pharmacological inhibition of prosurvival Bcl-2 with ABT-199
SL Khaw, D Mérino, MA Anderson, SP Glaser, P Bouillet, AW Roberts, DC Huang
Leukemia 2014
Cell death and the mitochondria: therapeutic targeting of the BCL-2 family-driven pathway: Therapeutic targeting of the BCL-2 family proteins
MJ Roy, A Vom, PE Czabotar, G Lessene
British Journal of Pharmacology 2014
Drp1 is dispensable for apoptotic cytochrome c release in primed MCF10A and fibroblast cells but affects Bcl-2 antagonist-induced respiratory changes: Drp1 is not required for ABT-737-induced apoptosis
P Clerc, SX Ge, H Hwang, J Waddell, BA Roelofs, M Karbowski, H Sesaki, BM Polster
British Journal of Pharmacology 2014
Radiosensitization by a novel Bcl-2 and Bcl-XL inhibitor S44563 in small-cell lung cancer
Y Loriot, P Mordant, D Dugue, O Geneste, A Gombos, P Opolon, J Guegan, JL Perfettini, A Pierre, LK Berthier, G Kroemer, JC Soria, S Depil, E Deutsch
Cell Death and Disease 2014
Putting the pieces together: How is the mitochondrial pathway of apoptosis regulated in cancer and chemotherapy?
R Elkholi, TT Renault, MN Serasinghe, JE Chipuk
Cancer & Metabolism 2014
An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity
FS Gazzaniga, EH Blackburn
Blood 2014
A Bim-targeting strategy overcomes adaptive bortezomib resistance in myeloma through a novel link between autophagy and apoptosis
S Chen, Y Zhang, L Zhou, Y Leng, H Lin, M Kmieciak, XY Pei, R Jones, RZ Orlowski, Y Dai, S Grant
Blood 2014
Maturation Stage of T-cell Acute Lymphoblastic Leukemia Determines BCL-2 versus BCL-XL Dependence and Sensitivity to ABT-199
TN Chonghaile, JE Roderick, C Glenfield, J Ryan, SE Sallan, LB Silverman, ML Loh, SP Hunger, B Wood, DJ DeAngelo, R Stone, M Harris, A Gutierrez, MA Kelliher, A Letai
Cancer Discovery 2014
B Cell Lymphoma-2 (BCL-2) Homology Domain 3 (BH3) Mimetics Demonstrate Differential Activities Dependent upon the Functional Repertoire of Pro- and Anti-apoptotic BCL-2 Family Proteins
TT Renault, R Elkholi, A Bharti, JE Chipuk
The Journal of biological chemistry 2014
Rational combination of dual PI3K/mTOR blockade and Bcl-2/-xL inhibition in AML
P Vachhani, P Bose, M Rahmani, S Grant
Physiological genomics 2014
Inhibition of Phosphatidylinositol 3-Kinase/AKT Signaling by NVP-BKM120 Promotes ABT-737-Induced Toxicity in a Caspase-Dependent Manner through Mitochondrial Dysfunction and DNA Damage Response in Established and Primary Cultured Glioblastoma Cells
EP Jane, DR Premkumar, A Morales, KA Foster, IF Pollack
The Journal of pharmacology and experimental therapeutics 2014
Apoptosis inducers in chronic lymphocytic leukemia.
Billard C
Oncotarget 2014
PUMA and BIM Are Required for Oncogene Inactivation–Induced Apoptosis
GR Bean, YT Ganesan, Y Dong, S Takeda, H Liu, PM Chan, Y Huang, LA Chodosh, GP Zambetti, JJ Hsieh, EH Cheng
Science signaling 2013
MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies
RV Sionov
ISRN Hematology 2013
ABT-199, a new Bcl-2-specific BH3 mimetic, has in vivo efficacy against aggressive Myc-driven mouse lymphomas without provoking thrombocytopenia
CJ Vandenberg, S Cory
Blood 2013
Emerging Drug Profile: Cyclin-Dependent Kinase Inhibitors
JS Blachly, JC Byrd
Leukemia & Lymphoma 2013
pRb/E2F-1-mediated caspase-dependent induction of Noxa amplifies the apoptotic effects of the Bcl-2/Bcl-xL inhibitor ABT-737
J Bertin-Ciftci, B Barré, JL Pen, L Maillet, C Couriaud, P Juin, F Braun
Cell Death and Differentiation 2013
Impact of bone marrow stromal cells on Bcl-2 family members in chronic lymphocytic leukemia
V Patel, K Balakrishnan, WG Wierda, V Gandhi
Leukemia & Lymphoma 2013
Decoding and unlocking the BCL-2 dependency of cancer cells
P Juin, O Geneste, F Gautier, S Depil, M Campone
Nature Reviews Cancer 2013
Bcl-2 antagonists: a proof of concept for CLL therapy
K Balakrishnan, V Gandhi
Investigational New Drugs 2013
Evaluation and critical assessment of putative MCL-1 inhibitors
S Varadarajan, M Vogler, M Butterworth, D Dinsdale, LD Walensky, GM Cohen
Cell Death and Differentiation 2013
Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy
PE Czabotar, G Lessene, A Strasser, JM Adams
Nature Reviews Molecular Cell Biology 2013
Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells
SG Katz, JL LaBelle, H Meng, RP Valeriano, JK Fisher, H Sun, SJ Rodig, SH Kleinstein, LD Walensky
Blood 2013
Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia
B Koss, J Morrison, RM Perciavalle, H Singh, JE Rehg, RT Williams, JT Opferman
Blood 2013
Priming BCL-2 to kill: the combination therapy of tamoxifen and ABT-199 in ER+ breast cancer
J Deng, A Letai
Breast Cancer Research 2013
BH3 profiling discriminates response to cytarabine-based treatment of acute myelogenous leukemia
WE Pierceall, SM Kornblau, NE Carlson, X Huang, N Blake, R Lena, M Elashoff, M Konopleva, MH Cardone, M Andreeff
Molecular cancer therapeutics 2013
Metastatic SW620 colon cancer cells are primed for death when detached and can be sensitized to anoikis by the BH3-mimetic ABT-737
A Maamer-Azzabi, O Ndozangue-Touriguine, J Bréard
Cell Death and Disease 2013
Modifying chemotherapy response by targeted inhibition of eukaryotic initiation factor 4A
R Cencic, F Robert, G Galicia-Vázquez, A Malina, K Ravindar, R Somaiah, P Pierre, J Tanaka, P Deslongchamps, J Pelletier
Blood Cancer Journal 2013
IP3R2 levels dictate the apoptotic sensitivity of diffuse large B-cell lymphoma cells to an IP3R-derived peptide targeting the BH4 domain of Bcl-2
H Akl, G Monaco, RL Rovere, K Welkenhuyzen, S Kiviluoto, T Vervliet, J Molgó, CW Distelhorst, L Missiaen, K Mikoshiba, JB Parys, HD Smedt, G Bultynck
Cell Death and Disease 2013
The sensitivity of diffuse large B-cell lymphoma cell lines to histone deacetylase inhibitor-induced apoptosis is modulated by BCL-2 family protein activity
RC Thompson, I Vardinogiannis, TD Gilmore
PloS one 2013
An evidence-based review of obatoclax mesylate in the treatment of hematological malignancies
CA Goard, AD Schimmer
Core evidence 2013
HA14-1, but not the BH3 mimetic ABT-737, causes Ca2+ dysregulation in platelets and human cell lines
H Akl, I Vandecaetsbeek, G Monaco, A Kauskot, T Luyten, K Welkenhuyzen, M Hoylaerts, HD Smedt, JB Parys, G Bultynck
Haematologica 2013
Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia
R Pan, LJ Hogdal, JM Benito, D Bucci, L Han, G Borthakur, J Cortes, DJ DeAngelo, L Debose, H Mu, H Döhner, VI Gaidzik, I Galinsky, LS Golfman, T Haferlach, KG Harutyunyan, J Hu, JD Leverson, G Marcucci, M Müschen, R Newman, E Park, PP Ruvolo, V Ruvolo, J Ryan, S Schindela, P Zweidler-McKay, RM Stone, H Kantarjian, M Andreeff, M Konopleva, AG Letai
Cancer Discovery 2013
Vinblastine rapidly induces NOXA and acutely sensitizes primary chronic lymphocytic leukemia cells to ABT-737
DJ Bates, AV Danilov, CH Lowrey, A Eastman
Molecular cancer therapeutics 2013
That which does not kill me makes me stronger; combining ERK1/2 pathway inhibitors and BH3 mimetics to kill tumour cells and prevent acquired resistance
MJ Sale, SJ Cook
British Journal of Pharmacology 2013
RNAi screening uncovers Dhx9 as a modifier of ABT-737 resistance in an Eμ-myc/Bcl-2 mouse model
JR Mills, A Malina, T Lee, DD Paola, O Larsson, C Miething, F Grosse, H Tang, M Zannis-Hadjopoulos, SW Lowe, J Pelletier
Blood 2013
ABT-199: A New Hope for Selective BCL-2 Inhibition
MS Davids, A Letai
Cancer Cell 2013
Customized chemotherapy in metastatic non-small cell lung cancer (NSCLC)
Jia Wei, Teresa Moran, Zhengyun Zou, Xiaoping Qian, Lifeng Wang, Carlos Camps, Wenjing Hu, Imane Chaib, Belén Sanchez, Lixia Xu, Niki Karachaliou, María Sanchez-Ronco, Baorui Liu, Rafael Rosell
Translational Lung Cancer Research 2013
TYK2–STAT1–BCL2 Pathway Dependence in T-cell Acute Lymphoblastic Leukemia
T Sanda, JW Tyner, A Gutierrez, VN Ngo, J Glover, BH Chang, A Yost, W Ma, AG Fleischman, W Zhou, Y Yang, M Kleppe, Y Ahn, J Tatarek, MA Kelliher, DS Neuberg, RL Levine, R Moriggl, M Müller, NS Gray, CH Jamieson, AP Weng, LM Staudt, BJ Druker, AT Look
Cancer Discovery 2013
mTOR Inhibition Specifically Sensitizes Colorectal Cancers with KRAS or BRAF Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1
AC Faber, EM Coffee, C Costa, A Dastur, H Ebi, AN Hata, AT Yeo, EJ Edelman, Y Song, AT Tam, JL Boisvert, RJ Milano, J Roper, DP Kodack, RK Jain, RB Corcoran, MN Rivera, S Ramaswamy, KE Hung, CH Benes, JA Engelman
Cancer Discovery 2013
Mitochondrial Bcl-2 family dynamics define therapy response and resistance in neuroblastoma
KC Goldsmith, M Gross, S Peirce, D Luyindula, X Liu, A Vu, M Sliozberg, R Guo, H Zhao, CP Reynolds, MD Hogarty
Cancer research 2012
Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells
D Mérino, SL Khaw, SP Glaser, DJ Anderson, LD Belmont, C Wong, P Yue, M Robati, B Phipson, WD Fairlie, EF Lee, KJ Campbell, CJ Vandenberg, S Cory, AW Roberts, MJ Ludlam, DC Huang, P Bouillet
Blood 2012
Decreased mitochondrial apoptotic priming underlies stroma-mediated treatment resistance in chronic lymphocytic leukemia
MS Davids, J Deng, A Wiestner, BJ Lannutti, L Wang, CJ Wu, WH Wilson, JR Brown, A Letai
Blood 2012
Targeting the B-Cell Lymphoma/Leukemia 2 Family in Cancer
MS Davids, A Letai
Journal of Clinical Oncology 2012
Glucocorticoid resistance in chronic lymphocytic leukaemia is associated with a failure of upregulated Bim/Bcl-2 complexes to activate Bax and Bak
T Melarangi, J Zhuang, K Lin, N Rockliffe, AG Bosanquet, M Oates, JR Slupsky, AR Pettitt
Cell Death and Disease 2012
Rapid Detection of an ABT-737-Sensitive Primed for Death State in Cells Using Microplate-Based Respirometry
P Clerc, GB Carey, Z Mehrabian, M Wei, H Hwang, GD Girnun, H Chen, SS Martin, BM Polster
PloS one 2012
Bcl-2 is a better ABT-737 target than Bcl-xL or Bcl-w and only Noxa overcomes resistance mediated by Mcl-1, Bfl-1, or Bcl-B
RW Rooswinkel, B de Kooij, M Verheij, J Borst
Cell Death and Disease 2012
The selective BH4-domain biology of Bcl-2-family members: IP3Rs and beyond
G Monaco, T Vervliet, H Akl, G Bultynck
Cellular and Molecular Life Sciences 2012
A Competitive Stapled Peptide Screen Identifies a Selective Small Molecule that Overcomes MCL-1-Dependent Leukemia Cell Survival
NA Cohen, ML Stewart, E Gavathiotis, JL Tepper, SR Bruekner, B Koss, JT Opferman, LD Walensky
Chemistry & Biology 2012
Biomarkers of Therapeutic Response to BCL2 Antagonists in Cancer
LT Lam, H Zhang, B Chyla
Molecular diagnosis & therapy 2012
Targeting the Bcl-2 family for cancer therapy
S Thomas, BA Quinn, SK Das, R Dash, L Emdad, S Dasgupta, XY Wang, P Dent, JC Reed, M Pellecchia, D Sarkar, PB Fisher
Expert Opinion on Therapeutic Targets 2012
Therapeutic effects of deleting cancer-associated fibroblasts in cholangiocarcinoma
JC Mertens, CD Fingas, JD Christensen, RL Smoot, SF Bronk, NW Werneburg, MP Gustafson, AB Dietz, LR Roberts, AE Sirica, GJ Gores
Cancer research 2012
Structural biology of the intrinsic cell death pathway: what do we know and what is missing?
EF Lee, WD Fairlie
Computational and Structural Biotechnology Journal 2012
ABT-737 induces Bim expression via JNK signaling pathway and its effect on the radiation sensitivity of HeLa cells
H Wang, YB Yang, HM Shen, J Gu, T Li, XM Li
PloS one 2012
Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism
M Rahmani, MM Aust, E Attkisson, DC Williams, A Ferreira-Gonzalez, S Grant
Cancer research 2012
B-lymphopoiesis is stopped by mobilizing doses of G-CSF and is rescued by overexpression of the anti-apoptotic protein Bcl2
IG Winkler, LJ Bendall, CE Forristal, F Helwani, B Nowlan, V Barbier, Y Shen, A Cisterne, LM Sedger, JP Levesque
Haematologica 2012
Understanding sensitivity to BH3 mimetics: ABT-737 as a case study to foresee the complexities of personalized medicine
VA Stamelos, CW Redman, A Richardson
Journal of molecular signaling 2012
BH3-only proteins in apoptosis at a glance
L Happo, A Strasser, S Cory
Journal of cell science 2012
ABT-737 synergizes with bortezomib to induce apoptosis, mediated by Bid cleavage, Bax activation, and mitochondrial dysfunction in an Akt-dependent context in malignant human glioma cell lines
DR Premkumar, EP Jane, JD DiDomenico, NA Vukmer, NR Agostino, IF Pollack
The Journal of pharmacology and experimental therapeutics 2012
BH3 profiling--measuring integrated function of the mitochondrial apoptotic pathway to predict cell fate decisions
VD Moore, A Letai
Cancer Letters 2012
BCL2 suppresses PARP1 function and nonapoptotic cell death
C Dutta, T Day, N Kopp, D Bodegom, MS Davids, J Ryan, L Bird, N Kommajosyula, O Weigert, A Yoda, H Fung, JR Brown, GI Shapiro, A Letai, DM Weinstock
Cancer research 2012
The Role of BCL2 Family of Apoptosis Regulator Proteins in Acute and Chronic Leukemias
F Tzifi, C Economopoulou, D Gourgiotis, A Ardavanis, S Papageorgiou, A Scorilas
Advances in Hematology 2012
Phosphoinositide 3-kinase/AKT/mTORC1/2 Signaling Determines Sensitivity of Burkitt's Lymphoma Cells to BH3 mimetics
LC Spender, GJ Inman
Molecular cancer research : MCR 2012
Targeting the regulatory machinery of BIM for cancer therapy.
Harada H, Grant S
Critical reviews in eukaryotic gene expression 2012
Sensitization of BCL-2–expressing breast tumors to chemotherapy by the BH3 mimetic ABT-737
SR Oakes, F Vaillant, E Lim, L Lee, K Breslin, F Feleppa, S Deb, ME Ritchie, E Takano, T Ward, SB Fox, D Generali, GK Smyth, A Strasser, DC Huang, JE Visvader, GJ Lindeman
Proceedings of the National Academy of Sciences 2011
Bcl-x(L) blocks a mitochondrial inner membrane channel and prevents Ca2+ overload-mediated cell death
D Tornero, I Posadas, V Ceña
PloS one 2011
Emerging Bcl-2 inhibitors for the treatment of cancer
AS Azmi, Z Wang, PA Philip, RM Mohammad, FH Sarkar
Expert Opinion on Emerging Drugs 2011
An antiapoptotic BCL-2 family expression index predicts the response of chronic lymphocytic leukemia to ABT-737
S Al-harbi, BT Hill, S Mazumder, K Singh, J DeVecchio, G Choudhary, LA Rybicki, M Kalaycio, JP Maciejewski, JA Houghton, A Almasan
Blood 2011
Inhibitors of the anti-apoptotic Bcl-2 proteins: a patent review
N Bajwa, C Liao, Z Nikolovska-Coleska
Expert Opinion on Therapeutic Patents 2011
Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia
D Sampath, C Liu, K Vasan, M Sulda, VK Puduvalli, WG Wierda, MJ Keating
Blood 2011
Multiple BH3 Mimetics Antagonize Antiapoptotic MCL1 Protein by Inducing the Endoplasmic Reticulum Stress Response and Up-regulating BH3-only Protein NOXA*
TC Albershardt, BL Salerni, RS Soderquist, DJ Bates, AA Pletnev, AF Kisselev, A Eastman
The Journal of biological chemistry 2011
Homoharringtonine reduced Mcl-1 expression and induced apoptosis in chronic lymphocytic leukemia
R Chen, L Guo, Y Chen, Y Jiang, WG Wierda, W Plunkett
Blood 2011
Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1–expressing myeloma cells
AA Morales, M Kurtoglu, SM Matulis, J Liu, D Siefker, DM Gutman, JL Kaufman, KP Lee, S Lonial, LH Boise
Blood 2011
Pretreatment Mitochondrial Priming Correlates with Clinical Response to Cytotoxic Chemotherapy
TN Chonghaile, KA Sarosiek, TT Vo, JA Ryan, A Tammareddi, VD Moore, J Deng, KC Anderson, P Richardson, YT Tai, CS Mitsiades, UA Matulonis, R Drapkin, R Stone, DJ Deangelo, DJ McConkey, SE Sallan, L Silverman, MS Hirsch, DR Carrasco, A Letai
Science (New York, N.Y.) 2011
SAR by Inter-Ligand nuclear Overhauser Effects (ILOEs) based discovery of acylsulfonamide compounds active against Bcl-xL and Mcl-1
MF Rega, B Wu, J Wei, Z Zhang, JF Cellitti, M Pellecchia
Journal of Medicinal Chemistry 2011
Decreased sensitivity of 17p-deleted chronic lymphocytic leukemia cells to a small molecule BCL-2 antagonist ABT-737
K Kojima, S Duvvuri, V Ruvolo, F Samaniego, A Younes, M Andreeff
Cancer 2011
Synergistic Activity of Fenretinide and the Bcl-2 Family Protein Inhibitor ABT-737 against Human Neuroblastoma
H Fang, TM Harned, O Kalous, V Maldonado, YA DeClerck, CP Reynolds
Clinical cancer research 2011
Substantial Susceptibility of Chronic Lymphocytic Leukemia to BCL2 Inhibition: Results of a Phase I Study of Navitoclax in Patients With Relapsed or Refractory Disease
AW Roberts, JF Seymour, JR Brown, WG Wierda, TJ Kipps, SL Khaw, DA Carney, SZ He, DC Huang, H Xiong, Y Cui, TA Busman, EM McKeegan, AP Krivoshik, SH Enschede, R Humerickhouse
Journal of Clinical Oncology 2011
Induction of Ca2+-driven apoptosis in chronic lymphocytic leukemia cells by peptide-mediated disruption of Bcl-2–IP3 receptor interaction
F Zhong, MW Harr, G Bultynck, G Monaco, JB Parys, HD Smedt, YP Rong, JK Molitoris, M Lam, C Ryder, S Matsuyama, CW Distelhorst
Blood 2010
The Beclin 1 interactome
C He, B Levine
Current Opinion in Cell Biology 2010
Bim-Bcl-2 homology 3 mimetic therapy is effective at suppressing inflammatory arthritis through the activation of myeloid cell apoptosis
JC Scatizzi, J Hutcheson, RM Pope, GS Firestein, AE Koch, M Mavers, A Smason, H Agrawal, GK 3rd, NS Chandel, RS Hotchkiss, H Perlman
Arthritis & Rheumatism 2010
Bax activation by engagement with, then release from, the BH3 binding site of Bcl-xL
F Gautier, Y Guillemin, PF Cartron, T Gallenne, N Cauquil, TL Diguarher, P Casara, FM Vallette, S Manon, JA Hickman, O Geneste, P Juin
Molecular and cellular biology 2010
Heightened mitochondrial priming is the basis for apoptotic hypersensitivity of CD4+ CD8+ thymocytes
JA Ryan, JK Brunelle, A Letai
Proceedings of the National Academy of Sciences 2010
Diminished sensitivity of chronic lymphocytic leukemia cells to ABT-737 and ABT-263 due to albumin binding in blood
M Vogler, SD Furdas, M Jung, T Kuwana, MJ Dyer, GM Cohen
Clinical cancer research 2010
Displacement of Bim by Bmf and Puma rather than increase in Bim level mediates paclitaxel-induced apoptosis in breast cancer cells
O Kutuk, A Letai
Cell Death and Differentiation 2010
Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1
D Yecies, NE Carlson, J Deng, A Letai
Blood 2010
Mitochondrial control of caspase-dependent and -independent cell death
LA Pradelli, M Bénéteau, JE Ricci
Cellular and Molecular Life Sciences 2010
Safety, Pharmacokinetics, Pharmacodynamics, and Activity of Navitoclax, a Targeted High Affinity Inhibitor of BCL-2, in Lymphoid Malignancies
WH Wilson, OA O'Connor, MS Czuczman, AS LaCasce, JF Gerecitano, JP Leonard, A Tulpule, K Dunleavy, H Xiong, YL Chiu, Y Cui, T Busman, SW Elmore, SH Rosenberg, AP Krivoshik, SH Enschede, RA Humerickhouse
The Lancet Oncology 2010
BH3 Domains other than Bim and Bid Can Directly Activate Bax/Bak*
H Du, J Wolf, B Schafer, T Moldoveanu, JE Chipuk, T Kuwana
The Journal of biological chemistry 2010
Inflammation and survival pathways: chronic lymphocytic leukemia as a model system
LS Chen, K Balakrishnan, V Gandhi
Biochemical Pharmacology 2010
The BH3 mimetic ABT-737 induces cancer cell senescence
JH Song, K Kandasamy, M Zemskova, YW Lin, AS Kraft
Cancer research 2010
The BCL-2 Family Reunion
JE Chipuk, T Moldoveanu, F Llambi, MJ Parsons, DR Green
Molecular Cell 2010
Phase I and Pharmacologic Study of SNS-032, a Potent and Selective Cdk2, 7, and 9 Inhibitor, in Patients With Advanced Chronic Lymphocytic Leukemia and Multiple Myeloma
WG Tong, R Chen, W Plunkett, D Siegel, R Sinha, RD Harvey, AZ Badros, L Popplewell, S Coutre, JA Fox, K Mahadocon, T Chen, P Kegley, U Hoch, WG Wierda
Journal of Clinical Oncology 2010
Small-Molecule Inhibitors of Protein-Protein Interactions
L Vassilev, D Fry
2010
A Bax-Mediated Mechanism for Obatoclax-Induced Apoptosis of Cholangiocarcinoma Cells
RL Smoot, BR Blechacz, NW Werneburg, SF Bronk, FA Sinicrope, AE Sirica, GJ Gores
Cancer research 2010
BH3-only proteins and their effects on cancer.
Vo TT, Letai A
Advances in experimental medicine and biology 2010
MCL-1-dependent leukemia cells are more sensitive to chemotherapy than BCL-2-dependent counterparts
JK Brunelle, J Ryan, D Yecies, JT Opferman, A Letai
The Journal of Cell Biology 2009
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009
The liver's dance with death: two Bcl-2 guardian proteins from the abyss
SC Cazanave, GJ Gores
Hepatology 2009
Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma
D Chauhan, AV Singh, B Ciccarelli, PG Richardson, MA Palladino, KC Anderson
Blood 2009
Bax activation by the BH3-only protein Puma promotes cell dependence on antiapoptotic Bcl-2 family members
T Gallenne, F Gautier, L Oliver, E Hervouet, B Noël, JA Hickman, O Geneste, PF Cartron, FM Vallette, S Manon, P Juin
The Journal of Cell Biology 2009
ABT-737 synergizes with chemotherapy to kill head and neck squamous cell carcinoma cells via a Noxa-mediated pathway
R Li, Y Zang, C Li, NS Patel, JR Grandis, DE Johnson
Molecular pharmacology 2009
Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia
R Chen, WG Wierda, S Chubb, RE Hawtin, JA Fox, MJ Keating, V Gandhi, W Plunkett
Blood 2009
Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics
MS Cragg, C Harris, A Strasser, CL Scott
Nature Reviews Cancer 2009
BH3 response profiles from neuroblastoma mitochondria predict activity of small molecule Bcl-2 family antagonists
KC Goldsmith, BJ Lestini, M Gross, L Ip, A Bhumbla, X Zhang, H Zhao, X Liu, MD Hogarty
Cell Death and Differentiation 2009
Bcl2 family proteins in carcinogenesis and the treatment of cancer
A Frenzel, F Grespi, W Chmelewskij, A Villunger
Apoptosis 2009
Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy
MH Kang, CP Reynolds
Clinical cancer research 2009
Chronic Lymphocytic Leukemia and B and T Cells Differ in Their Response to Cyclic Nucleotide Phosphodiesterase Inhibitors
JA Meyers, DW Su, A Lerner
Journal of immunology (Baltimore, Md. : 1950) 2009
Bim Upregulation by Histone Deacetylase Inhibitors Mediates Interactions with the Bcl-2 Antagonist ABT-737: Evidence for Distinct Roles for Bcl-2, Bcl-xL, and Mcl-1
S Chen, Y Dai, XY Pei, S Grant
Molecular and cellular biology 2009
Control of mitochondrial apoptosis by the Bcl-2 family
JK Brunelle, A Letai
Journal of cell science 2009
PUMA cooperates with direct activator proteins to promote mitochondrial outer membrane permeabilization and apoptosis.
Chipuk JE, Green DR
Cell cycle (Georgetown, Tex.) 2009
EPO receptor circuits for primary erythroblast survival
P Sathyanarayana, A Dev, J Fang, E Houde, O Bogacheva, O Bogachev, M Menon, S Browne, A Pradeep, C Emerson, DM Wojchowski
Blood 2008
Bim and Bmf in tissue homeostasis and malignant disease
JD Piñon, V Labi, A Egle, A Villunger
Oncogene 2008
ABT-737 induces expression of the death receptor 5 and sensitizes human cancer cells to TRAIL-induced apoptosis
JH Song, K Kandasamy, AS Kraft
The Journal of biological chemistry 2008
Mechanism of apoptosis induction by inhibition of the anti-apoptotic BCL-2 proteins
JE Chipuk, JC Fisher, CP Dillon, RW Kriwacki, T Kuwana, DR Green
Proceedings of the National Academy of Sciences 2008
In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas
KD Mason, CJ Vandenberg, CL Scott, AH Wei, S Cory, DC Huang, AW Roberts
Proceedings of the National Academy of Sciences 2008
AT-101 induces apoptosis in CLL B cells and overcomes stromal cell-mediated Mcl-1 induction and drug resistance
K Balakrishnan, JA Burger, WG Wierda, V Gandhi
Blood 2008
Surface expression of Bcl-2 in chronic lymphocytic leukemia and other B-cell leukemias and lymphomas without a breakpoint t(14;18)
BA McCarthy, E Boyle, XP Wang, D Guzowski, S Paul, R Catera, J Trott, X Yan, CM Croce, R Damle, S Yancopoulos, BT Messmer, M Lesser, SL Allen, KR Rai, N Chiorazzi
Molecular Medicine 2008
Gossypol, a BH3 mimetic, induces apoptosis in chronic lymphocytic leukemia cells
K Balakrishnan, WG Wierda, MJ Keating, V Gandhi
Blood 2008
BH3 mimetic ABT-737 potentiates TRAIL-mediated apoptotic signaling by unsequestering Bim and Bak in human pancreatic cancer cells
S Huang, FA Sinicrope
Cancer research 2008
Preclinical studies of Apogossypolone: a new nonpeptidic pan small-molecule inhibitor of Bcl-2, Bcl-XL and Mcl-1 proteins in Follicular Small Cleaved Cell Lymphoma model
AA Arnold, A Aboukameel, J Chen, D Yang, S Wang, A Al-Katib, RM Mohammad
Molecular Cancer 2008
Postnatal developmental regulation of Bcl-2 family proteins in brain mitochondria
L Soane, ZT Siegel, RA Schuh, G Fiskum
Journal of Neuroscience Research 2008
Targeting the Bcl-2-regulated apoptosis pathway by BH3 mimetics: a breakthrough in anticancer therapy?
V Labi, F Grespi, F Baumgartner, A Villunger
Cell Death and Differentiation 2008
How do BCL-2 proteins induce mitochondrial outer membrane permeabilization?
JE Chipuk, DR Green
Trends in Cell Biology 2008
Mimicking the BH3 domain to kill cancer cells
TN Chonghaile, A Letai
Oncogene 2008
Alteration of the Mitochondrial Apoptotic Pathway Is Key to Acquired Paclitaxel Resistance and Can Be Reversed by ABT-737
O Kutuk, A Letai
Cancer research 2008
Small-molecule Bcl-2 antagonists as targeted therapy in oncology.
Warr MR, Shore GC
Current oncology (Toronto, Ont.) 2008
Bcl-2-regulated apoptosis: mechanism and therapeutic potential
JM Adams, S Cory
Current Opinion in Immunology 2007
BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia
VD Moore, KD Schlis, SE Sallan, SA Armstrong, A Letai
Blood 2007
Induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomas
Y Gong, R Somwar, K Politi, M Balak, J Chmielecki, X Jiang, W Pao
PLoS Medicine 2007
BH3 mimetics to improve cancer therapy; mechanisms and examples
L Zhang, L Ming, J Yu
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 2007
The cancer cell’s “power plants” as promising therapeutic targets: An overview
PL Pedersen
Journal of Bioenergetics and Biomembranes 2007

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