ApoList – December 2018


Multidomain Bcl-2 family proteins

Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia – Adriana E. Tron, Matthew A. Belmonte, Ammar Adam, Brian M. Aquila, Lawrence H. Boise, Elisabetta Chiarparin, Justin Cidado, Kevin J. Embrey, Eric Gangl, Francis D. Gibbons, Gareth P. Gregory, David Hargreaves, J. Adam Hendricks, Jeffrey W. Johannes, Ricky W. Johnstone, Steven L. Kazmirski, Jason G. Kettle, Michelle L. Lamb, Shannon M. Matulis, Ajay K. Nooka, Martin J. Packer, Bo Peng, Philip B. Rawlins, Daniel W. Robbins, Alwin G. Schuller, Nancy Su, Wenzhan Yang, Qing Ye, Xiaolan Zheng, J. Paul Secrist, Edwin A. Clark, David M. Wilson, Stephen E. Fawell and Alexander W. Hird. https://www.nature.com/articles/s41467-018-07551-w

Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia – Courtney D. DiNardo, Keith Pratz, Vinod Pullarkat, Brian A. Jonas, Martha Arellano, Pamela S. Becker, Olga Frankfurt, Marina Konopleva, Andrew H. Wei, Hagop M. Kantarjian, Tu Xu, Wan-Jen Hong, Brenda Chyla, Jalaja Potluri, Daniel A. Pollyea and Anthony Letai. http://bloodjournal.org/content/133/1/7.abstract?etoc

BH3-mimetic toolkit guides the respective use of BCL2 and MCL1 BH3-mimetics in myeloma treatment – Patricia Gomez-Bougie, Sophie Maiga, Benoît Tessoulin, Jessie Bourcier, Antoine Bonnet, Manuel S. Rodriguez, Steven Le Gouill, Cyrille Touzeau, Philippe Moreau, Catherine Pellat-Deceunynck and Martine Amiot. http://bloodjournal.org/content/132/25/2656.abstract?etoc

Genetic biomarkers predict response to dual BCL-2 and MCL-1 targeting in acute myeloid leukaemia cells – Martin Grundy, Sahana Balakrishnan, Matthew Fox, Claire H. Seedhouse and  Nigel H. Russell. http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=26540&path[]=82570

Variable BCL2/BCL2L1 ratio in multiple myeloma with t(11;14) – Alice Cleynen, Mehmet Samur, Aurore Perrot, Laure Buisson, Sabrina Maheo, Mariateresa Fulciniti, Michel Attal, Nikhil Munshi, Hervé Avet-Loiseau and Jill Corre. http://bloodjournal.org/content/132/26/2778?etoc

Targeting BCL-xL improves the efficacy of bromodomain and extra-terminal protein inhibitors in triple-negative breast cancer by eliciting the death of senescent cells – Sylvia S. Gayle, Jennifer M. Sahni, Bryan M. Webb, Kristen L. Weber-Bonk, Melyssa S. Shively, Raffaella Spina, Eli E. Bar, Matthew K. Summers and Ruth A. Keri. http://www.jbc.org/content/early/2018/11/27/jbc.RA118.004712.abstract

HOXC6 promotes cervical cancer progression via regulation of Bcl-2 – Yongsheng Wang, Cong Wang, Na Liu, Jun Hou, Wenjing Xiao and Hui Wang. https://www.fasebj.org/doi/abs/10.1096/fj.201801099RR?ai=ts&ui=ly8&af=T

NOTCH1 Represses MCL-1 Levels in GSI-resistant T-ALL, Making them Susceptible to ABT-263 – Anahita Dastur, AHyun Choi, Carlotta Costa, Xunqin Yin, August Williams, Joseph McClanaghan, Max Greenberg, Justine Roderick, Neha U. Patel, Jessica Boisvert, Ultan McDermott, Mathew J. Garnett, Jorge Almenara, Steven Grant, Kathryn Rizzo, Jeffrey A. Engelman, Michelle Kelliher, Anthony C. Faber and Cyril H. Benes. http://clincancerres.aacrjournals.org/content/25/1/31

Targeted inhibition of PI3Kα/δ is synergistic with BCL-2 blockade in genetically defined subtypes of DLBCL – Kamil Bojarczuk, Kirsty Wienand, Jeremy A. Ryan, Linfeng Chen, Mariana Villalobos-Ortiz, Elisa Mandato, Joanna Stachura, Anthony Letai, Lee N. Lawton, Bjoern Chapuy and Margaret A. Shipp. http://bloodjournal.org/content/133/1/70.abstract?etoc

BH3-only proteins

Spatiotemporal Control of CNS Myelination by Oligodendrocyte Programmed Cell Death through the TFEB-PUMA Axis – Lu O. Sun, Sara B. Mulinyawe, Hannah Y. Collins, Adiljan Ibrahim, Qingyun Li, David J. Simon, Marc Tessier-Lavigne, Ben A. Barres. https://www.cell.com/cell/fulltext/S0092-8674(18)31400-4?dgcid=raven_jbs_etoc_email

Lymphocyte-Specific Chromatin Accessibility Pre-determines Glucocorticoid Resistance in Acute Lymphoblastic Leukemia [Bim] – Duohui Jing, Yizhou Huang, Xiaoyun Liu, Keith C.S. Sia, Julia C. Zhang, Xiaolu Tai, Meng Wang, Cara E. Toscan, Hannah McCalmont, Kathryn Evans, Chelsea Mayoh, Rebecca C. Poulos, Miriam Span, Jianqing Mi, Chao Zhang, Jason W.H. Wong, Dominik Beck, John E. Pimanda, Richard B. Lock. https://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30523-3

Mouse ER+/PIK3CAH1047R breast cancers caused by exogenous estrogen are heterogeneously dependent on estrogen and undergo BIM-dependent apoptosis with BH3 and PI3K agents – Elias E. Stratikopoulos, Nicole Kiess, Matthias Szabolcs, Sarah Pegno, Cheung Kakit, Xuewei Wu, Poulikos I. Poulikakos, Pamela Cheung, Hank Schmidt and Ramon Parsons. https://www.nature.com/articles/s41388-018-0436-4?

Death receptors

Herpes simplex virus 1 ICP6 impedes TNF receptor 1-induced necrosome assembly during compartmentalization to detergent-resistant membrane vesicles – Mohammad Ali, Linda Roback and Edward S. Mocarski. http://www.jbc.org/content/early/2018/11/30/jbc.RA118.004651.abstract

Caspase-8 and FLIP

RIPK1 and Caspase-8 Ensure Chromosome Stability Independently of Their Role in Cell Death and Inflammation – Gianmaria Liccardi, Laura Ramos Garcia, Tencho Tenev, Alessandro Annibaldi, Arnaud J. Legrand, David Robertson, Rebecca Feltham, Holly Anderton, Maurice Darding, Nieves Peltzer, Marius Dannappel, Hannah Schünke, Luca L. Fava, Manuel D. Haschka, Timo Glatter, Alexey Nesvizhskii, Alexander Schmidt, Philip A. Harris, John Bertin, Peter J. Gough, Andreas Villunger, John Silke, Manolis Pasparakis, Katiuscia Bianchi, Pascal Meier. https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30980-8

Regulated proteolysis of p62/SQSTM1 enables differential control of autophagy and nutrient sensing – Julia Sanchez-Garrido, Vanessa Sancho-Shimizu and Avinash R. Shenoy. http://stke.sciencemag.org/content/11/559/eaat6903

TLR-stimulated IRAKM activates caspase-8 inflammasome in microglia and promotes neuroinflammation – Cun-Jin Zhang, Meiling Jiang, Hao Zhou, Weiwei Liu, Chenhui Wang, Zizhen Kang, Bing Han, Quanri Zhang, Xing Chen, Jianxin Xiao, Amanda Fisher, William J. Kaiser, Masanori A. Murayama, Yoichiro Iwakura, Ji Gao, Julie Carman, Ashok Dongre, George Dubyak, Derek W. Abbott, Fu-Dong Shi, Richard M. Ransohoff and Xiaoxia Li. https://www.jci.org/articles/view/121901

Induction of immunosuppressive functions and NF-κB by FLIP in monocytes – Alessandra Fiore, Stefano Ugel, Francesco De Sanctis, Sara Sandri, Giulio Fracasso, Rosalinda Trovato, Silvia Sartoris, Samantha Solito, Susanna Mandruzzato, Fulvia Vascotto, Keli L. Hippen, Giada Mondanelli, Ursula Grohmann, Geny Piro, Carmine Carbone, Davide Melisi, Rita T. Lawlor, Aldo Scarpa, Alessia Lamolinara, Manuela Iezzi, Matteo Fassan, Silvio Bicciato, Bruce R. Blazar, Ugur Sahin, Peter J. Murray and Vincenzo Bronte. https://www.nature.com/articles/s41467-018-07654-4


Single-cell analysis of pyroptosis dynamics reveals conserved GSDMD-mediated subcellular events that precede plasma membrane rupture – Nathalia M. de Vasconcelos, Nina Van Opdenbosch, Hanne Van Gorp, Eef Parthoens and Mohamed Lamkanfi. https://www.nature.com/articles/s41418-018-0106-7

Inflammation / Efferocytosis

Molecular mechanisms of biogenesis of apoptotic exosome-like vesicles and their roles as damage-associated molecular patterns – Soo Jeong Park, Jeong Mi Kim, Jihyo Kim, Jaehark Hur, Sun Park, Kyongmin Kim, Ho-Joon Shin and Yong-Joon Chwae. https://www.pnas.org/content/115/50/E11721?etoc=

Efferocytosis Fuels Requirements of Fatty Acid Oxidation and the Electron Transport Chain to Polarize Macrophages for Tissue Repair – Shuang Zhang, Samuel Weinberg, Matthew DeBerge, Anastasiia Gainullina, Matthew Schipma, Jason M. Kinchen, Issam Ben-Sahra, David R. Gius, Laurent Yvan- Charvet, Navdeep S. Chandel, Paul T. Schumacker, Edward B. Thorp. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30741-1#%20

Treatment-Induced Tumor Cell Apoptosis and Secondary Necrosis Drive Tumor Progression in the Residual Tumor Microenvironment through MerTK and IDO1 – Thomas A. Werfel, David L. Elion, Bushra Rahman, Donna J. Hicks, Violeta Sanchez, Paula I. Gonzales-Ericsson, Mellissa J. Nixon, Jamaal L. James, Justin M. Balko, Peggy A. Scherle, Holly K. Koblish and Rebecca S. Cook. http://cancerres.aacrjournals.org/content/79/1/171


The SMAC mimetic LCL-161 displays antitumor activity in preclinical models of rituximab-resistant B-cell lymphoma – Kyle Runckel, Matthew J. Barth, Cory Mavis, Juan J. Gu and Francisco J. Hernandez-Ilizaliturri. http://www.bloodadvances.org/content/2/23/3516.abstract?etoc

Dimerization and auto-processing induce caspase-11 protease activation within the non-canonical inflammasome – Connie Ross, Amy H Chan, Jessica Von Pein, Dave Boucher and Kate Schroder. http://life-science-alliance.org/content/1/6/e201800237.abstract

ATP Synthase C-Subunit-Deficient Mitochondria Have a Small Cyclosporine A-Sensitive Channel, but Lack the Permeability Transition Pore – Maria A. Neginskaya, Maria E. Solesio, Elena V. Berezhnaya, Giuseppe F. Amodeo, Nelli Mnatsakanyan, Elizabeth A. Jonas, Evgeny V. Pavlov. https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31963-6


BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines – Delphine Merino, Gemma L. Kelly, Guillaume Lessene, Andrew H. Wei, Andrew W. Roberts, Andreas Strasser. https://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30525-7

The Structural Basis of Necroptotic Cell Death Signaling – Emma J. Petrie, Peter E. Czabotar, James M. Murphy. https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(18)30229-9

Role and Regulation of Pro-survival BCL-2 Proteins in Multiple Myeloma – Anne Slomp and Victor Peperzak. https://www.frontiersin.org/articles/10.3389/fonc.2018.00533/full


Special issue on Necroinflammation



* Death and fire: the concept of necroinflammation – Andreas Linkermann

* Necroptosis in anti-viral inflammation – Himani Nailwal and Francis Ka-Ming Chan

* Ferroptosis and necroinflammation, a yet poorly explored link – Bettina Proneth and Marcus Conrad

* Programmed Necrosis and Disease:We interrupt your regular programming to bring you necroinflammation – Eui Ho Kim, Sing-Wai Wong and Jennifer Martinez

* Crashing the computer: apoptosis vs. necroptosis in neuroinflammation – Bradlee L. Heckmann, Bart Tummers and Douglas R. Green

* Necroinflammation emerges as a key regulator of hematopoiesis in health and disease – Philipp J. Jost and Ulrike Höckendorf

* Paving the way for precision medicine v2.0 in intensive care by profiling necroinflammation in biofluids – Tom Vanden Berghe and Eric Hoste

* Pyroptosis versus necroptosis: similarities, differences, and crosstalk – Daniel Frank and James E. Vince

* Comparing the effects of different cell death programs in tumor progression and immunotherapy – Michelle N. Messmer, Annelise G. Snyder and Andrew Oberst


Macrophages regulate the clearance of living cells by calreticulin – Dmitri V. Krysko, Kodi S. Ravichandran and Peter Vandenabeele. https://www.nature.com/articles/s41467-018-06807-9

Glucocorticoid Resistance in Acute Lymphoblastic Leukemia: BIM Finally – Jessie A. Brown, Adolfo Ferrando. https://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30532-4

Venetoclax in AML: aiming for “just right” – Laura C. Michaelis. http://bloodjournal.org/content/133/1/3?etoc


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