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Citations to this article

Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance
Laura Bonapace, … , Martin Stanulla, Jean-Pierre Bourquin
Laura Bonapace, … , Martin Stanulla, Jean-Pierre Bourquin
Published March 1, 2010
Citation Information: J Clin Invest. 2010;120(4):1310-1323. https://doi.org/10.1172/JCI39987.
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Research Article Oncology

Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance

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Abstract

In vivo resistance to first-line chemotherapy, including to glucocorticoids, is a strong predictor of poor outcome in children with acute lymphoblastic leukemia (ALL). Modulation of cell death regulators represents an attractive strategy for subverting such drug resistance. Here we report complete resensitization of multidrug-resistant childhood ALL cells to glucocorticoids and other cytotoxic agents with subcytotoxic concentrations of obatoclax, a putative antagonist of BCL-2 family members. The reversal of glucocorticoid resistance occurred through rapid activation of autophagy-dependent necroptosis, which bypassed the block in mitochondrial apoptosis. This effect was associated with dissociation of the autophagy inducer beclin-1 from the antiapoptotic BCL-2 family member myeloid cell leukemia sequence 1 (MCL-1) and with a marked decrease in mammalian target of rapamycin (mTOR) activity. Consistent with a protective role for mTOR in glucocorticoid resistance in childhood ALL, combination of rapamycin with the glucocorticoid dexamethasone triggered autophagy-dependent cell death, with characteristic features of necroptosis. Execution of cell death, but not induction of autophagy, was strictly dependent on expression of receptor-interacting protein (RIP-1) kinase and cylindromatosis (turban tumor syndrome) (CYLD), two key regulators of necroptosis. Accordingly, both inhibition of RIP-1 and interference with CYLD restored glucocorticoid resistance completely. Together with evidence for a chemosensitizing activity of obatoclax in vivo, our data provide a compelling rationale for clinical translation of this pharmacological approach into treatments for patients with refractory ALL.

Authors

Laura Bonapace, Beat C. Bornhauser, Maike Schmitz, Gunnar Cario, Urs Ziegler, Felix K. Niggli, Beat W. Schäfer, Martin Schrappe, Martin Stanulla, Jean-Pierre Bourquin

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Citations to this article (162)

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The inducible role of autophagy in cell death: emerging evidence and future perspectives
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Cell Communication and Signaling : CCS 2025
The histone methyltransferase KMT2D maintains cellular glucocorticoid responsiveness by shielding the glucocorticoid receptor from degradation
Wu CJ, Livak F, Ashwell JD
The Journal of Biological Chemistry 2024
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Olivas-Aguirre M, Pérez-Chávez J, Torres-López L, Hernández-Cruz A, Pottosin I, Dobrovinskaya O
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The Interplay Between Autophagy and Regulated Necrosis
Zhang L, Cui T, Wang X
Antioxidants & Redox Signaling 2023
Microphysiological Drug-Testing Platform for Identifying Responses to Prodrug Treatment in Primary Leukemia.
Gökçe F, Kaestli A, Lohasz C, de Geus M, Kaltenbach HM, Renggli K, Bornhauser B, Hierlemann A, Modena M
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Induction of autophagy-dependent ferroptosis to eliminate drug-tolerant human retinoblastoma cells
K Liu, J Huang, J Liu, D Klionsky, R Kang, D Tang
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Jin X, Wang J
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Construction of a novel signature and prediction of the immune landscape in gastric cancer based on necroptosis-related genes.
Li Z, Yang W, Liu D, Ye W, Du G, Li X
Scientific Reports 2022
Autophagy in Hematological Malignancies.
García Ruiz O, Sánchez-Maldonado JM, López-Nevot MÁ, García P, Macauda A, Hernández-Mohedo F, González-Sierra PA, Martínez-Bueno M, Pérez E, Reyes-Zurita FJ, Campa D, Canzian F, Jurado M, Rodríguez-Sevilla JJ, Sainz J
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Chronic oligodendrocyte injury in central nervous system pathologies
Molina-Gonzalez I, Miron VE, Antel JP
2022
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
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Autophagy 2021
Understanding the Role of Autophagy in Cancer Formation and Progression Is a Real Opportunity to Treat and Cure Human Cancers
S Patergnani, S Missiroli, G Morciano, M Perrone, CM Mantovani, G Anania, F Fiorica, P Pinton, C Giorgi
Cancers 2021
Overcoming Glucocorticoid Resistance in Acute Lymphoblastic Leukemia: Repurposed Drugs Can Improve the Protocol
M Olivas-Aguirre, L Torres-López, I Pottosin, O Dobrovinskaya
Frontiers in Oncology 2021
Targeting Drug Chemo-Resistance in Cancer Using Natural Products
WH Talib, AR Alsayed, M Barakat, MI Abu-Taha, AI Mahmod
Biomedicines 2021
Mechanism of interaction between autophagy and apoptosis in cancer
S Das, N Shukla, SS Singh, S Kushwaha, R Shrivastava
Apoptosis 2021
Cell death pathways: intricate connections and disease implications
M Kist, D Vucic
The EMBO Journal 2021
Accumulation of Abnormal Amyloplasts in Pulp Cells Induces Bitter Pit in Malus domestica
L Qiu, S Hu, Y Wang, H Qu
Frontiers in Plant Science 2021
MiRNA-124 regulates the sensitivity of renal cancer cells to cisplatin-induced necroptosis by targeting the CAPN4-CNOT3 axis
Q Mao, Q Zhuang, J Shen, Z Chen, D Xue, T Ding, X He
Translational andrology and urology 2021
Pan-Caspase Inhibitor zVAD Induces Necroptotic and Autophagic Cell Death in TLR3/4-Stimulated Macrophages
Chen YS, Chuang WC, Kung HN, Cheng CY, Huang DY, Sekar P, Lin WW
Molecules and Cells 2021
Autophagy Function and Regulation in Kidney Disease
GP Kaushal, K Chandrashekar, LA Juncos, SV Shah
Biomolecules 2020

The Underlying Role of Mitophagy in Different Regulatory Mechanisms of Chronic Obstructive Pulmonary Disease


JY Liu, MY Zhang, YQ Qu
International journal of chronic obstructive pulmonary disease 2020
Role of Autophagy in Cancer Cell Response to Nucleolar and Endoplasmic Reticulum Stress
A Pecoraro, M Pagano, G Russo, A Russo
International journal of molecular sciences 2020
Reversal of glucocorticoid resistance in paediatric acute lymphoblastic leukaemia is dependent on restoring BIM expression
CE Toscan, D Jing, C Mayoh, RB Lock
British Journal of Cancer 2020
The Role of Necroptosis in ROS-Mediated Cancer Therapies and Its Promising Applications
SK Hsu, WT Chang, IL Lin, YF Chen, NB Padalwar, KC Cheng, YN Teng, CH Wang, CC Chiu
Cancers 2020
Nanomaterial-mediated autophagy: coexisting hazard and health benefits in biomedicine
X Feng, Y Zhang, C Zhang, X Lai, Y Zhang, J Wu, C Hu, L Shao
Particle and Fibre Toxicology 2020
TNFR2 is required for RIP1-dependent cell death in human leukemia
J Aguadé-Gorgorió, S McComb, C Eckert, A Guinot, B Marovca, C Mezzatesta, S Jenni, L Abduli, M Schrappe, MP Dobay, M Stanulla, A von Stackelberg, G Cario, JP Bourquin, BC Bornhauser
Blood Advances 2020
Integrative genomic analyses reveal mechanisms of glucocorticoid resistance in acute lymphoblastic leukemia
RJ Autry, SW Paugh, R Carter, L Shi, J Liu, DC Ferguson, CE Lau, EJ Bonten, W Yang, JR McCorkle, JA Beard, JC Panetta, JD Diedrich, KR Crews, D Pei, CJ Coke, S Natarajan, A Khatamian, SE Karol, E Lopez-Lopez, B Diouf, C Smith, Y Gocho, K Hagiwara, KG Roberts, S Pounds, SM Kornblau, W Stock, EM Paietta, MR Litzow, H Inaba, CG Mullighan, S Jeha, CH Pui, C Cheng, D Savic, J Yu, C Gawad, MV Relling, JJ Yang, WE Evans
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Targeting Autophagy for Cancer Treatment and Tumor Chemosensitization
M Pérez-Hernández, A Arias, D Martínez-García, R Pérez-Tomás, R Quesada, V Soto-Cerrato
Cancers 2019
A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy
R Khandia, M Dadar, A Munjal, K Dhama, K Karthik, R Tiwari, MI Yatoo, HM Iqbal, KP Singh, SK Joshi, W Chaicumpa
Cells 2019
Therapeutic Modulation of Autophagy in Leukaemia and Lymphoma
M Djavaheri-Mergny, S Giuriato, MP Tschan, M Humbert
Cells 2019

The molecular mechanisms underlying BCR/ABL degradation in chronic myeloid leukemia cells promoted by Beclin1-mediated autophagy


X Huang, Y Li, L Shou, L Li, Z Chen, X Ye, W Qian
Cancer management and research 2019
miR-221/222-Mediated Inhibition of Autophagy Promotes Dexamethasone Resistance in Multiple Myeloma
J Xu, Y Su, A Xu, F Fan, S Mu, L Chen, Z Chu, B Zhang, H Huang, J Zhang, J Deng, L Ai, C Sun, Y Hu
Molecular Therapy 2019
Exploiting Necroptosis for Therapy of Acute Lymphoblastic Leukemia
C Mezzatesta, BC Bornhauser
Frontiers in Cell and Developmental Biology 2019
IgG4-Related Sclerosing Disease Causing Spinal Cord Compression: The First Reported Case in Literature
N Merza, A Taha, J Lung, AW Benderman, SE Wright
Case Reports in Immunology 2019
GX15–070 (Obatoclax), a Bcl-2 family proteins inhibitor engenders apoptosis and pro-survival autophagy and increases Chemosensitivity in neuroblastoma
S Cournoyer, A Addioui, A Belounis, M Beaunoyer, C Nyalendo, RL Gall, P Teira, E Haddad, G Vassal, H Sartelet
BMC Cancer 2019
Targeting BCL2 in Chronic Lymphocytic Leukemia and Other Hematologic Malignancies
FF Yalniz, WG Wierda
Drugs 2019
Proteasome Inhibition by Carfilzomib Induced Apotosis and Autophagy in a T-cell Acute Lymphoblastic Leukemia Cell Line
Maryam Sadat Hosseini, Mohammad Hossein Mohammadi, Rouhollah Vahabpour Roudsari, Leila Jafari, Pargol Mashati, Ahmad Gharehbaghian
IRAN J PHARM RES 2019
Diverse autophagy and apoptosis in myeloid leukemia cells induced by 20(s)-GRh2 and blue LED irradiation
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RSC Advances 2019
Molecular mechanisms contributing to glucocorticoid resistance in lymphoid malignancies.
Scheijen B
Cancer drug resistance (Alhambra, Calif.) 2019
The independence of and associations among apoptosis, autophagy, and necrosis
Q Chen, J Kang, C Fu
Signal Transduction and Targeted Therapy 2018
Autophagy, selective autophagy, and necroptosis in COPD
K Mizumura, S Maruoka, T Shimizu, Y Gon
International journal of chronic obstructive pulmonary disease 2018
Obatoclax and Paclitaxel Synergistically Induce Apoptosis and Overcome Paclitaxel Resistance in Urothelial Cancer Cells
R Jiménez-Guerrero, J Gasca, M Flores, B Pérez-Valderrama, C Tejera-Parrado, R Medina, M Tortolero, F Romero, M Japón, C Sáez
Cancers 2018
AT 101 induces early mitochondrial dysfunction and HMOX1 (heme oxygenase 1) to trigger mitophagic cell death in glioma cells
N Meyer, S Zielke, JB Michaelis, B Linder, V Warnsmann, S Rakel, HD Osiewacz, S Fulda, M Mittelbronn, C Münch, C Behrends, D Kögel
Autophagy 2018
Necrostatin-1 Attenuates Cisplatin-Induced Nephrotoxicity Through Suppression of Apoptosis and Oxidative Stress and Retains Klotho Expression
Y Ning, Y Shi, J Chen, N Song, J Cai, Y Fang, X Yu, J Ji, X Ding
Frontiers in pharmacology 2018
Targeting autophagy for combating chemoresistance and radioresistance in glioblastoma
MA Taylor, BC Das, SK Ray
Apoptosis 2018
Modes of cell death induced by tetrahydroisoquinoline-based analogs in MDA-MB-231 breast and A549 lung cancer cell lines
M Nel, A Joubert, W Dohle, B Potter, A Theron
Drug design, development and therapy 2018
Ionophores: Potential Use as Anticancer Drugs and Chemosensitizers
V Kaushik, J Yakisich, A Kumar, N Azad, A Iyer
Cancers 2018
Bypassing drug resistance by triggering necroptosis: recent advances in mechanisms and its therapeutic exploitation in leukemia
X Huang, F Xiao, Y Li, W Qian, W Ding, X Ye
Journal of Experimental & Clinical Cancer Research 2018
Therapeutic Implications of Autophagy Inducers in Immunological Disorders, Infection, and Cancer
S Byun, E Lee, KW Lee
International journal of molecular sciences 2017
Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer
WJ Wei, ZK Sun, CT Shen, HJ Song, XY Zhang, ZL Qiu, QY Luo
Theranostics 2017
Natural Compounds As Modulators of Non-apoptotic Cell Death in Cancer Cells
L Guaman-Ortiz, M Orellana, E Ratovitski
Current genomics 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
CYLD Deubiquitinase Negatively Regulates High Glucose-Induced NF- κ B Inflammatory Signaling in Mesangial Cells
Y Li, W Huang, Y Xu, L Zhou, Y Liang, C Gao, Y Long, Y Xu
BioMed Research International 2017
Autophagy is required for cell survival under L-asparaginase-induced metabolic stress in acute lymphoblastic leukemia cells
H Takahashi, J Inoue, K Sakaguchi, M Takagi, S Mizutani, J Inazawa
Oncogene 2017
Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia
V Frismantas, MP Dobay, A Rinaldi, J Tchinda, SH Dunn, J Kunz, P Richter-Pechanska, B Marovca, O Pail, S Jenni, E Diaz-Flores, BH Chang, TJ Brown, RH Collins, S Uhrig, GP Balasubramanian, OR Bandapalli, S Higi, S Eugster, P Voegeli, M Delorenzi, G Cario, ML Loh, M Schrappe, M Stanulla, AE Kulozik, MU Muckenthaler, V Saha, JA Irving, R Meisel, T Radimerski, AV Stackelberg, C Eckert, JW Tyner, P Horvath, BC Bornhauser, JP Bourquin
Blood 2017
Targeting Autophagy in ALK-Associated Cancers
J Frentzel, D Sorrentino, S Giuriato
Cancers 2017
Autophagy in Cancer Therapy
S Fulda
Frontiers in Oncology 2017
Matrine induces RIP3-dependent necroptosis in cholangiocarcinoma cells
B Xu, M Xu, Y Tian, Q Yu, Y Zhao, X Chen, P Mi, H Cao, B Zhang, G Song, Y Zhan, T Hu
Cell Death Discovery 2017
Shikonin-induced necroptosis is enhanced by the inhibition of autophagy in non-small cell lung cancer cells
HJ Kim, KE Hwang, DS Park, SH Oh, HY Jun, KH Yoon, ET Jeong, HR Kim, YS Kim
Journal of Translational Medicine 2017
Differential regulation of cell death pathways by the microenvironment correlates with chemoresistance and survival in leukaemia
MY Qattan, EY Bakker, R Rajendran, DW Chen, V Saha, J Liu, L Zeef, JM Schwartz, L Mutti, C Demonacos, M Krstic-Demonacos, D Tang
PloS one 2017
MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma
J Xiong, L Wang, XC Fei, XF Jiang, Z Zheng, Y Zhao, CF Wang, B Li, SJ Chen, A Janin, RP Gale, WL Zhao
Blood Cancer Journal 2017
Combing oncolytic adenovirus expressing Beclin-1 with chemotherapy agent doxorubicin synergistically enhances cytotoxicity in human CML cells in vitro
L Li, L You, L Mao, S Jin, X Chen, W Qian
Acta Pharmacologica Sinica 2017
BH3 mimetic Obatoclax (GX15-070) mediates mitochondrial stress predominantly via MCL-1 inhibition and induces autophagy-dependent necroptosis in human oral cancer cells
P Sulkshane, T Teni
Oncotarget 2017
The mechanisms of graphene-based materials-induced programmed cell death: a review of apoptosis, autophagy, and programmed necrosis
L Ou, S Lin, B Song, J Liu, R Lai, L Shao
International Journal of Nanomedicine 2017
Relevance of necroptosis in cancer
N Lalaoui, G Brumatti
Immunology and Cell Biology 2017
Autophagy: Friend or Foe in Lung Disease?
Kenji Mizumura, Suzanne Cloonan, Mary E Choi, Shu Hashimoto, Kiichi Nakahira, Stefan W Ryter, Augustine M K Choi
Annals of the American Thoracic Society 2016
Autophagy in acute kidney injury
GP Kaushal, SV Shah
Kidney International 2016
MEK Inhibition Sensitizes Precursor B-Cell Acute Lymphoblastic Leukemia (B-ALL) Cells to Dexamethasone through Modulation of mTOR Activity and Stimulation of Autophagy
A Polak, P Kiliszek, T Sewastianik, M Szydłowski, E Jabłońska, E Białopiotrowicz, P Górniak, S Markowicz, E Nowak, MA Grygorowicz, M Prochorec-Sobieszek, D Nowis, J Gołąb, S Giebel, E Lech-Marańda, K Warzocha, P Juszczyński, JI Park
PloS one 2016
The autophagy-lysosomal system in subarachnoid haemorrhage
H Wu, H Niu, C Wu, Y Li, K Wang, J Zhang, Y Wang, S Yang
Journal of Cellular and Molecular Medicine 2016
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
DJ Klionsky, K Abdelmohsen, A Abe, MJ Abedin, H Abeliovich, AA Arozena, H Adachi, CM Adams, PD Adams, K Adeli, PJ Adhihetty, SG Adler, G Agam, R Agarwal, MK Aghi, M Agnello, P Agostinis, PV Aguilar, J Aguirre-Ghiso, EM Airoldi, S Ait-Si-Ali, T Akematsu, ET Akporiaye, M Al-Rubeai, GM Albaiceta, C Albanese, D Albani, ML Albert, J Aldudo, H Algül, M Alirezaei, I Alloza, A Almasan, M Almonte-Beceril, ES Alnemri, C Alonso, N Altan-Bonnet, DC Altieri, S Alvarez, L Alvarez-Erviti, S Alves, G Amadoro, A Amano, C Amantini, S Ambrosio, I Amelio, AO Amer, M Amessou, A Amon, Z An, FA Anania, SU Andersen, UP Andley, CK Andreadi, N Andrieu-Abadie, A Anel, DK Ann, S Anoopkumar-Dukie, M Antonioli, H Aoki, N Apostolova, S Aquila, K Aquilano, K Araki, E Arama, A Aranda, J Araya, A Arcaro, E Arias, H Arimoto, AR Ariosa, JL Armstrong, T Arnould, I Arsov, K Asanuma, V Askanas, E Asselin, R Atarashi, SS Atherton, JD Atkin, LD Attardi, P Auberger, G Auburger, L Aurelian, R Autelli, L Avagliano, ML 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Autophagy 2016
Inhibition of regulated cell death by cell-penetrating peptides
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Cellular and Molecular Life Sciences 2016
Comparison of in vitro antileukemic activity of obatoclax and ABT-737
M Opydo-Chanek, L Mazur
Tumor Biology 2016
Necroptosis: an alternative cell death program defending against cancer
D Chen, J Yu, L Zhang
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2016
Cancer therapy in the necroptosis era
Z Su, Z Yang, L Xie, JP DeWitt, Y Chen
Cell Death and Differentiation 2016
Necroptosis Is an Important Severity Determinant and Potential Therapeutic Target in Experimental Severe Pancreatitis
JM Louhimo, ML Steer, G Perides
CMGH Cellular and Molecular Gastroenterology and Hepatology 2016
Silencing Livin induces apoptotic and autophagic cell death, increasing chemotherapeutic sensitivity to cisplatin of renal carcinoma cells
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Tumor Biology 2016
Cancer and necroptosis: friend or foe?
S Philipp, J Sosna, D Adam
Cellular and Molecular Life Sciences 2016
Autophagy is associated with cucurbitacin D-induced apoptosis in human T cell leukemia cells
T Nakanishi, Y Song, C He, D Wang, K Morita, J Tsukada, T Kanazawa, Y Yoshida
Medical Oncology 2016
5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Inhibits RIPK1/RIPK3-Dependent Necroptosis in THP-1-Derived Foam Cells
F Tian, J Yao, M Yan, X Sun, W Wang, W Gao, Z Tian, S Guo, Z Dong, B Li, T Gao, P Shan, B Liu, H Wang, J Cheng, Q Gao, Z Zhang, W Cao, Y Tian
Scientific Reports 2016
Relationship between triterpenoid anticancer drug resistance, autophagy, and caspase-1 in adult T-cell leukemia
T Nakanishi, Y Song, C He, D Wang, K Morita, J Tsukada, T Kanazawa, Y Yoshida
PeerJ 2016
The BH3 Mimetic Obatoclax Accumulates in Lysosomes and Causes Their Alkalinization
VA Stamelos, N Fisher, H Bamrah, C Voisey, JC Price, WE Farrell, CW Redman, A Richardson, A Villunger
PloS one 2016
Akt/AMPK/mTOR pathway was involved in the autophagy induced by vitamin E succinate in human gastric cancer SGC-7901 cells
Y Yu, L Hou, H Song, P Xu, Y Sun, K Wu
Molecular and Cellular Biochemistry 2016
Effects of a novel β–lapachone derivative on Trypanosoma cruzi: Parasite death involving apoptosis, autophagy and necrosis
DO Anjos, ES Alves, VT Gonçalves, SS Fontes, ML Nogueira, AM Suarez-Fontes, JB da Costa, F Rios-Santos, MA Vannier-Santos
International Journal for Parasitology Drugs and Drug Resistance 2016
Necroptosis in tumorigenesis, activation of anti-tumor immunity, and cancer therapy
MB Meng, HH Wang, YL Cui, ZQ Wu, YY Shi, NG Zaorsky, L Deng, ZY Yuan, Y Lu, P Wang
Oncotarget 2016
Wogonin induces Beclin-1/PI3K and reactive oxygen species-mediated autophagy in human pancreatic cancer cells
SJ Li, SJ Sun, J Gao, FB Sun
Oncology Letters 2016
Smac mimetic LCL161 overcomes protective ER stress induced by obatoclax, synergistically causing cell death in multiple myeloma
V Ramakrishnan, M Gomez, V Prasad, T Kimlinger, U Painuly, B Mukhopadhyay, J Haug, L Bi, SV Rajkumar, S Kumar
Oncotarget 2016
Pan-Bcl-2 inhibitor Obatoclax is a potent late stage autophagy inhibitor in colorectal cancer cells independent of canonical autophagy signaling
BC Koehler, A Jassowicz, AL Scherr, S Lorenz, P Radhakrishnan, N Kautz, C Elssner, J Weiss, D Jaeger, M Schneider, H Schulze-Bergkamen
BMC Cancer 2015
Glucocorticoid Signaling
JC Wang, C Harris
Glucocorticoid Signaling 2015
Protective Macroautophagy Is Involved in Vitamin E Succinate Effects on Human Gastric Carcinoma Cell Line SGC-7901 by Inhibiting mTOR Axis Phosphorylation
L Hou, Y Li, H Song, Z Zhang, Y Sun, X Zhang, K Wu, YJ Wang
PloS one 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
Autophagy collaborates with ubiquitination to downregulate oncoprotein E2A/Pbx1 in B-cell acute lymphoblastic leukemia
N Yuan, L Song, W Lin, Y Cao, F Xu, S Liu, A Zhang, Z Wang, X Li, Y Fang, H Zhang, W Zhao, S Hu, J Wang, S Zhang
Blood Cancer Journal 2015
Untangling knots between autophagic targets and candidate drugs, in cancer therapy
T Xie, SJ Li, MR Guo, Y Wu, HY Wang, K Zhang, X Zhang, L Ouyang, J Liu
Cell Proliferation 2015
Cell death by autophagy: emerging molecular mechanisms and implications for cancer therapy
S Fulda, D Kögel
Oncogene 2015
Differential roles of RIPK1 and RIPK3 in TNF-induced necroptosis and chemotherapeutic agent-induced cell death
K Moriwaki, J Bertin, PJ Gough, GM Orlowski, FK Chan
Cell Death and Disease 2015
Aging and uremia: Is there cellular and molecular crossover?
WE White
World Journal of Nephrology 2015
Interferon Regulatory Factor-1 Signaling Regulates the Switch between Autophagy and Apoptosis to Determine Breast Cancer Cell Fate
JL Schwartz-Roberts, KL Cook, C Chen, AN Shajahan-Haq, M Axelrod, A Warri, RB Riggins, L Jin, BR Haddad, BV Kallakury, WT Baumann, R Clarke
Cancer research 2015
CYLD Regulates Noscapine Activity in Acute Lymphoblastic Leukemia via a Microtubule-Dependent Mechanism
Y Yang, J Ran, L Sun, X Sun, Y Luo, B Yan, Tala, M Liu, D Li, L Zhang, G Bao, J Zhou
Theranostics 2015
Cell death induction by the BH3 mimetic GX15-070 in thyroid carcinoma cells
M Broecker-Preuss, J Viehof, H Jastrow, N Becher-Boveleth, D Fuhrer, K Mann
Journal of Experimental & Clinical Cancer Research 2015
Targeting mTOR/p70S6K/glycolysis signaling pathway restores glucocorticoid sensitivity to 4E-BP1 null Burkitt Lymphoma
L Gu, L Xie, C Zuo, Z Ma, Y Zhang, Y Zhu, J Gao
BMC Cancer 2015
Genomics and drug profiling of fatal TCF3-HLF−positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options
U Fischer, M Forster, A Rinaldi, T Risch, S Sungalee, HJ Warnatz, B Bornhauser, M Gombert, C Kratsch, AM Stütz, M Sultan, J Tchinda, CL Worth, V Amstislavskiy, N Badarinarayan, A Baruchel, T Bartram, G Basso, C Canpolat, G Cario, H Cavé, D Dakaj, M Delorenzi, MP Dobay, C Eckert, E Ellinghaus, S Eugster, V Frismantas, S Ginzel, OA Haas, O Heidenreich, G Hemmrich-Stanisak, K Hezaveh, JI Höll, S Hornhardt, P Husemann, P Kachroo, CP Kratz, G Kronnie, B Marovca, F Niggli, AC McHardy, AV Moorman, R Panzer-Grümayer, BS Petersen, B Raeder, M Ralser, P Rosenstiel, D Schäfer, M Schrappe, S Schreiber, M Schütte, B Stade, R Thiele, N der Weid, A Vora, M Zaliova, L Zhang, T Zichner, M Zimmermann, H Lehrach, A Borkhardt, JP Bourquin, A Franke, JO Korbel, M Stanulla, ML Yaspo
Nature Genetics 2015
Tissue acidosis induces neuronal necroptosis via ASIC1a channel independent of its ionic conduction: ( A1 ) Electron microscopy images of neurons treated with pH 7.4 (left) or pH 6.0 solution (middle and right). Of 57 cells counted in the pH 6.0-treated samples, 47 showed morphology similar to that shown in the middle and right panels. For pH 7.4-treated samples, the majority of cells had a similar morphology to that shown in the left panel; only 3 out of the 41 cells examined showed morphology that resembled that in the middle panel. ( A2 ) Enlarged images from the white boxes in A1 showing swelling of organelles in pH 6.0- but not pH 7.4-treated neurons. ( B ) PcTX1 (10 nM) and Nec-1 (20 μM), but not BHA (100 μM), BEL (30 μM), DPI (15 μM), RTO (25 μM), CHX (100 μM), or z-VAD-fmk (10 μM), rescued cells from acid-induced neuronal death (indicated by the dashed line) (n=4–12, ***pC1) Rescue from acid-induced neuronal death by 20 μM Nec-1 (propidium iodide [PI] staining assay). ( C2 ) Summary data for C1 . At least 200 neurons were counted for each condition (***pD) Knockdown efficiency of RIP1 shRNA as determined by Western blotting (***pE) Rescue of acid-induced neuronal death by RIP1 shRNA (CTB assay, n=3, ***p
YZ Wang, JJ Wang, Y Huang, F Liu, WZ Zeng, Y Li, ZG Xiong, MX Zhu, TL Xu
eLife 2015
Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD
Kenji Mizumura, Suzanne Cloonan, Kiichi Nakahira, Abhiram R. Bhashyam, Morgan Cervo, Tohru Kitada, Kimberly Glass, Caroline Owen, Ashfaq Mahmood, George Washko, Shu Hashimoto, Stefan Ryter, Augustine M. K. Choi
Journal of Clinical Investigation 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
Targeting SQSTM1/p62 Induces Cargo Loading Failure and Converts Autophagy to Apoptosis via NBK/Bik
S Chen, L Zhou, Y Zhang, Y Leng, XY Pei, H Lin, R Jones, RZ Orlowski, Y Dai, S Grant
Molecular and cellular biology 2014
Targeting the mitochondrial apoptotic pathway: a preferred approach in hematologic malignancies?
K Brinkmann, H Kashkar
Cell Death and Disease 2014
Human Cancer Growth and Therapy in Immunodeficient Mouse Models
LD Shultz, N Goodwin, F Ishikawa, V Hosur, BL Lyons, DL Greiner
Cold Spring Harbor Protocols 2014
Mcl-1 ubiquitination: unique regulation of an essential survival protein
B Mojsa, I Lassot, S Desagher
Cells 2014
The Impact of Autophagy on Cell Death Modalities
SW Ryter, K Mizumura, AM Choi
International Journal of Cell Biology 2014
Targeting the apoptosis pathway in hematologic malignancies
S Zaman, R Wang, V Gandhi
Leukemia & Lymphoma 2014
Taking aim at Alzheimer's disease through the mammalian target of rapamycin
K Maiese
Annals of Medicine 2014
Autosis and autophagic cell death: the dark side of autophagy
Y Liu, B Levine
Cell Death and Differentiation 2014
Autophagy in the physiology and pathology of the central nervous system
V Nikoletopoulou, ME Papandreou, N Tavernarakis
Cell Death and Differentiation 2014
Cell and Molecular Determinants of In Vivo Efficacy of the BH3 Mimetic ABT-263 against Pediatric Acute Lymphoblastic Leukemia Xenografts
S Suryani, H Carol, TN Chonghaile, V Frismantas, C Sarmah, L High, B Bornhauser, MJ Cowley, B Szymanska, K Evans, I Boehm, E Tonna, L Jones, DM Manesh, RT Kurmasheva, C Billups, W Kaplan, A Letai, JP Bourquin, PJ Houghton, MA Smith, RB Lock
Clinical cancer research 2014
Anticancer Agents Targeted to Sirtuins
T Kozako, T Suzuki, M Yoshimitsu, N Arima, S Honda, S Soeda
Molecules (Basel, Switzerland) 2014
Assessment of the effect of sphingosine kinase inhibitors on apoptosis,unfolded protein response and autophagy of T-cell acute lymphoblastic leukemia cells; indications for novel therapeutics
Evangelisti C, Evangelisti C, Teti G, Chiarini F, Falconi M, Melchionda F, Pession A, Bertaina A, Locatelli F, McCubrey JA, Beak DJ, Bittman R, Pyne S, Pyne NJ, Martelli AM
Oncotarget 2014
WISP1: Clinical Insights for a Proliferative and Restorative Member of the CCN Family
Maiese K
Current neurovascular research 2014
RFX1–dependent activation of SHP-1 induces autophagy by a novel obatoclax derivative in hepatocellular carcinoma cells
Su JC, Tseng PH, Hsu CY, Tai WT, Huang JW, Ko CH, Lin MW, Liu CY, Chen KF, Shiau CW
Oncotarget 2014
Image-based RNA interference screening reveals an individual dependence of acute lymphoblastic leukemia on stromal cysteine support
Boutter J, Huang Y, Marovca B, Vonderheit A, Grotzer MA, Eckert C, Cario G, Wollscheid B, Horvath P, Bornhauser BC, Bourquin JP
Oncotarget 2014
Cutting through the complexities of mTOR for the treatment of stroke.
Maiese K
Current neurovascular research 2014
Inhibiting autophagy potentiates the anticancer activity of IFN1@/IFNα in chronic myeloid leukemia cells
S Zhu, L Cao, Y Yu, L Yang, M Yang, K Liu, J Huang, R Kang, KM Livesey, D Tang
Autophagy 2013
MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies
RV Sionov
ISRN Hematology 2013
Photoreceptor cell death and rescue in retinal detachment and degenerations
Y Murakami, S Notomi, T Hisatomi, T Nakazawa, T Ishibashi, JW Miller, DG Vavvas
Progress in Retinal and Eye Research 2013
Glucocorticoids and Osteocyte Autophagy
W Yao, W Dai, JX Jiang, NE Lane
Bone 2013
An evidence-based review of obatoclax mesylate in the treatment of hematological malignancies
CA Goard, AD Schimmer
Core evidence 2013
A JNK-mediated autophagy pathway that triggers c-IAP degradation and necroptosis for anticancer chemotherapy
W He, Q Wang, B Srinivasan, J Xu, MT Padilla, Z Li, X Wang, Y Liu, X Gou, HM Shen, C Xing, Y Lin
Oncogene 2013
Obatoclax (GX15-070) triggers necroptosis by promoting the assembly of the necrosome on autophagosomal membranes
F Basit, S Cristofanon, S Fulda
Cell Death and Differentiation 2013
Placental autophagy regulation by the BOK-MCL1 rheostat
M Kalkat, J Garcia, J Ebrahimi, M Melland-Smith, T Todros, M Post, I Caniggia
Autophagy 2013
BECN1 and BIM interactions with MCL-1 determine fludarabine resistance in leukemic B cells
A Sharma, K Singh, S Mazumder, BT Hill, M Kalaycio, A Almasan
Cell Death and Disease 2013
The mechanism of necroptosis in normal and cancer cells
S Fulda
Cancer biology & therapy 2013
Potent obatoclax cytotoxicity and activation of triple death mode killing across infant acute lymphoblastic leukemia
KA Urtishak, AY Edwards, LS Wang, A Hudome, BW Robinson, JS Barrett, K Cao, L Cory, JS Moore, AD Bantly, QC Yu, IM Chen, SR Atlas, CL Willman, M Kundu, AJ Carroll, NA Heerema, M Devidas, JM Hilden, ZE Dreyer, SP Hunger, GH Reaman, CA Felix
Blood 2013
Identification of novel predictor classifiers for inflammatory bowel disease by gene expression profiling
T Montero-Meléndez, X Llor, E García-Planella, M Perretti, A Suárez
PloS one 2013
The synergism of MCL1 and glycolysis on pediatric acute lymphoblastic leukemia cell survival and prednisolone resistance
IM Ariës, BR Hansen, T Koch, R Dungen, WE Evans, R Pieters, ML Boer
Haematologica 2013
Shikonin kills glioma cells through necroptosis mediated by RIP-1
C Huang, Y Luo, J Zhao, F Yang, H Zhao, W Fan, P Ge
PloS one 2013
Potent antitumor activity of oncolytic adenovirus expressing Beclin-1 via induction of autophagic cell death in leukemia
Tong Y, You L, Liu H, Li L, Meng H, Qian Q, Qian W
Oncotarget 2013
Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosis
SA Saddoughi, S Gencer, YK Peterson, KE Ward, A Mukhopadhyay, J Oaks, J Bielawski, ZM Szulc, RJ Thomas, SP Selvam, CE Senkal, E Garrett-Mayer, RM de Palma, D Fedarovich, A Liu, AA Habib, RV Stahelin, D Perrotti, B Ogretmen
EMBO Molecular Medicine 2012
Staurosporine Induces Necroptotic Cell Death under Caspase-Compromised Conditions in U937 Cells
ZA Dunai, G Imre, G Barna, T Korcsmaros, I Petak, PI Bauer, R Mihalik
PloS one 2012
Efficacy of the investigational mTOR kinase inhibitor MLN0128 / INK128 in models of B-cell acute lymphoblastic leukemia
MR Janes, C Vu, S Mallya, M Shieh, JJ Limon, LS Li, KA Jessen, MB Martin, P Ren, MB Lilly, L Sender, Y Liu, C Rommel, DA Fruman
Leukemia 2012
The Role of mTOR Inhibitors for the Treatment of B-Cell Lymphomas
P Argyriou, P Economopoulou, S Papageorgiou
Advances in Hematology 2012
Inhibition of Bcl-2 antiapoptotic members by obatoclax potently enhances sorafenib-induced apoptosis in human myeloid leukemia cells through a Bim-dependent process
M Rahmani, MM Aust, E Attkisson, DC Williams, A Ferreira-Gonzalez, S Grant
Blood 2012
Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia: Current and Emerging Treatments
A Martin, E Morgan, N Hijiya
Pediatric Drugs 2012
Attenuation of TNFSF10/TRAIL-induced apoptosis by an autophagic survival pathway involving TRAF2- and RIPK1/RIP1-mediated MAPK8/JNK activation
W He, Q Wang, J Xu, X Xu, MT Padilla, G Ren, X Gou, Y Lin
Autophagy 2012
Copy number aberrations of BCL2 and CDKN2A/B identified by array-CGH in thymic epithelial tumors
I Petrini, PS Meltzer, PA Zucali, J Luo, C Lee, A Santoro, HS Lee, KJ Killian, Y Wang, M Tsokos, M Roncalli, SM Steinberg, Y Wang, G Giaccone
Cell Death and Disease 2012
Two hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment
Martelli AM, Chiarini F, Evangelisti C, Cappellini A, Buontempo F, Bressanin D, Fini M, McCubrey JA
Oncotarget 2012
Glucocorticoid dose determines osteocyte cell fate
J Jia, W Yao, M Guan, W Dai, M Shahnazari, R Kar, L Bonewald, JX Jiang, NE Lane
The FASEB Journal 2011
Autophagy: for better or for worse
E Wirawan, TV Berghe, S Lippens, P Agostinis, P Vandenabeele
Cell Research 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
Autophagy and apoptosis- what’s the connection?
JM Gump, A Thorburn
Trends in Cell Biology 2011
Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies
W Alduaij, A Ivanov, J Honeychurch, EJ Cheadle, S Potluri, SH Lim, K Shimada, CH Chan, A Tutt, SA Beers, MJ Glennie, MS Cragg, TM Illidge
Blood 2011
Necroptosis: Biochemical, Physiological and Pathological Aspects
Z Dunai, PI Bauer, R Mihalik
Pathology & Oncology Research 2011
Autophagic activity in cortical neurons under acute oxidative stress directly contributes to cell death
GC Higgins, RJ Devenish, PM Beart, P Nagley
Cellular and Molecular Life Sciences 2011
Necroptosis, necrostatins and tissue injury
CC Smith, DM Yellon
Journal of Cellular and Molecular Medicine 2011
Noninvasive bioluminescent imaging of primary patient acute lymphoblastic leukemia: a strategy for preclinical modeling
DM Barrett, AE Seif, C Carpenito, DT Teachey, JD Fish, CH June, SA Grupp, GS Reid
Blood 2011
A comprehensive glossary of autophagy-related molecules and processes (2 nd edition)
DJ Klionsky, EH Baehrecke, JH Brumell, CT Chu, P Codogno, AM Cuervo, J Debnath, V Deretic, Z Elazar, EL Eskelinen, S Finkbeiner, J Fueyo-Margareto, DA Gewirtz, M Jäättelä, G Kroemer, B Levine, TJ Melia, N Mizushima, DC Rubinsztein, A Simonsen, A Thorburn, M Thumm, SA Tooze
Autophagy 2011
zVAD-induced autophagic cell death requires c-Src-dependent ERK and JNK activation and reactive oxygen species generation
SY Chen, LY Chiu, MC Ma, JS Wang, CL Chien, WW Lin
Autophagy 2011
Optimization of Circulating Biomarkers of Obatoclax-Induced Cell Death in Patients with Small Cell Lung Cancer
Dean EJ, Cummings J, Roulston A, Berger M, Ranson M, Blackhall F, Dive C
Neoplasia (New York, N.Y.) 2011
Smac Mimetic Bypasses Apoptosis Resistance in FADD- or Caspase-8-Deficient Cells by Priming for Tumor Necrosis Factor α-Induced Necroptosis
Laukens B, Jennewein C, Schenk B, Vanlangenakker N, Schier A, Cristofanon S, Zobel K, Deshayes K, Vucic D, Jeremias I, Bertrand MJ, Vandenabeele P, Fulda S
Neoplasia (New York, N.Y.) 2011
Obatoclax induces Atg7-dependent autophagy independent of beclin-1 and BAX/BAK
F McCoy, J Hurwitz, N McTavish, I Paul, C Barnes, B O'Hagan, K Odrzywol, J Murray, D Longley, G McKerr, DA Fennell
Cell Death and Disease 2010
GX15-070 (obatoclax) overcomes glucocorticoid resistance in acute lymphoblastic leukemia through induction of apoptosis and autophagy
N Heidari, MA Hicks, H Harada
Cell Death and Disease 2010
The mammalian target of rapamycin inhibitor RAD001 (everolimus) synergizes with chemotherapeutic agents, ionizing radiation and proteasome inhibitors in pre-B acute lymphocytic leukemia
P Saunders, A Cisterne, J Weiss, KF Bradstock, LJ Bendall
Haematologica 2010
Novel Approaches to Prevent Leukemia Relapse Following Allogeneic Hematopoietic Cell Transplantation
MR Verneris, MJ Burke
Current Hematologic Malignancy Reports 2010
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

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