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Anthony G. Letai, MD, PhD


Medical Oncology

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Physician

  • Physician
  • Associate Professor of Medicine, Harvard Medical School

Centers/Programs

Clinical Interests

  • Leukemias

Contact Information

  • Appointments617-632-6140
  • Office Phone Number617-632-2348
  • Fax617-582-8160

Bio

Dr. Letai received his MD and PhD from the University of Chicago. He completed his residency in internal medicine at Brigham and Women's Hospital, and a fellowship in hematology and oncology at DFCI. He did his postdoctoral research training in the laboratory of Dr. Stanley Korsmeyer. Dr. Letai's research focuses on the mechanisms by which cancer cells evade death, and on the application of that knowledge to the selective killing of cancer cells. He joined the faculty of DFCI and Harvard Medical School in 2004.

Board Certification:

  • Medical Oncology, 2001

Fellowship:

  • Dana-Farber/Partners CancerCare, Hematology/Oncology

Residency:

  • Brigham and Women's Hospital, Internal Medicine

Medical School:

  • University of Chicago

Recent Awards:

  • Leukemia and Lymphoma Society Scholar Award 2008
  • American Society of Clinical Investigation, Elected Member 2009
  • V Scholar Award 2005
  • Smith Family New Investigator 2004
  • Kimmel Scholar Award 2005

Research

Dysregulation of Death Pathways in Cancer

The cells of the body are constructed so that if they become sufficiently damaged or abnormal, programmed cell death, or apoptosis, rapidly eliminates them before they can cause any harm. Cancer cells, which bear many abnormalities, apparently have found ways to escape this death sentence. One way that cancer cells escape death is via the overexpression of antideath proteins in the BCL-2 family. We are investigating how these antideath proteins might be selectively targeted in cancer cells. Using a combination of mouse models, protein biochemistry, and mitochondrial and cellular studies, we have determined conditions under which cancer and normal cells are susceptible to inhibition of BCL-2 family function. We are collaborating with biotechnology and pharmaceutical firms to bring small-molecule BCL-2 antagonists to clinical trial here at Dana-Farber. Most likely, the novel strategy of BCL-2 antagonism will first be tested in chronic lymphocytic leukemia, small-cell lung cancer, and non-Hodgkin's lymphoma. If these trials are successful, the strategy of BCL-2 antagonism may find wide application in other human cancers.We also investigate more fundamental questions about how interactions among BCL-2 family proteins govern death and survival in normal and cancer cells. We explore how these proteins participate in a wide range of death signals, growth factor withdrawal, and chemotherapy.

Gutierrez-Martinez P, Hogdal L, Nagai M, Kruta M, Singh R, Sarosiek K, Nussenzweig A, Beerman I, Letai A, Rossi DJ. Diminished apoptotic priming and ATM signalling confer a survival advantage onto aged haematopoietic stem cells in response to DNA damage. Nat Cell Biol. 2018 Apr; 20(4):413-421.
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Brown FC, Still E, Koche RP, Yim CY, Takao S, Cifani P, Reed C, Gunasekera S, Ficarro SB, Romanienko P, Mark W, McCarthy C, de Stanchina E, Gonen M, Seshan V, Bhola P, O'Donnell C, Spitzer B, Stutzke C, Lavallée VP, Hébert J, Krivtsov AV, Melnick A, Paietta EM, Tallman MS, Letai A, Sauvageau G, Pouliot G, Levine R, Marto JA, Armstrong SA, Kentsis A. MEF2C Phosphorylation Is Required for Chemotherapy Resistance in Acute Myeloid Leukemia. Cancer Discov. 2018 Apr; 8(4):478-497.
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Rezaei Araghi R, Bird GH, Ryan JA, Jenson JM, Godes M, Pritz JR, Grant RA, Letai A, Walensky LD, Keating AE. Iterative optimization yields Mcl-1-targeting stapled peptides with selective cytotoxicity to Mcl-1-dependent cancer cells. Proc Natl Acad Sci U S A. 2018 Jan 30; 115(5):E886-E895.
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DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, Arellano M, Frattini MG, Kantarjian H, Popovic R, Chyla B, Xu T, Dunbar M, Agarwal SK, Humerickhouse R, Mabry M, Potluri J, Konopleva M, Pollyea DA. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Feb; 19(2):216-228.
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Terai H, Kitajima S, Potter DS, Matsui Y, Quiceno LG, Chen T, Kim TJ, Rusan M, Thai TC, Piccioni F, Donovan KA, Kwiatkowski N, Hinohara K, Wei G, Gray NS, Fischer ES, Wong KK, Shimamura T, Letai A, Hammerman PS, Barbie DA. ER Stress Signaling Promotes the Survival of Cancer "Persister Cells" Tolerant to EGFR Tyrosine Kinase Inhibitors. Cancer Res. 2018 Feb 15; 78(4):1044-1057.
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Lagares D, Santos A, Grasberger PE, Liu F, Probst CK, Rahimi RA, Sakai N, Kuehl T, Ryan J, Bhola P, Montero J, Kapoor M, Baron M, Varelas X, Tschumperlin DJ, Letai A, Tager AM. Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis. Sci Transl Med. 2017 Dec 13; 9(420).
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Leverson JD, Sampath D, Souers AJ, Rosenberg SH, Fairbrother WJ, Amiot M, Konopleva M, Letai A. Found in Translation: How Preclinical Research Is Guiding the Clinical Development of the BCL2-Selective Inhibitor Venetoclax. Cancer Discov. 2017 12; 7(12):1376-1393.
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Saito Y, Mochizuki Y, Ogahara I, Watanabe T, Hogdal L, Takagi S, Sato K, Kaneko A, Kajita H, Uchida N, Fukami T, Shultz LD, Taniguchi S, Ohara O, Letai AG, Ishikawa F. Overcoming mutational complexity in acute myeloid leukemia by inhibition of critical pathways. Sci Transl Med. 2017 Oct 25; 9(413).
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Carné Trécesson S, Souazé F, Basseville A, Bernard AC, Pécot J, Lopez J, Bessou M, Sarosiek KA, Letai A, Barillé-Nion S, Valo I, Coqueret O, Guette C, Campone M, Gautier F, Juin PP. BCL-XL directly modulates RAS signalling to favour cancer cell stemness. Nat Commun. 2017 Oct 24; 8(1):1123.
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Mai WX, Gosa L, Daniels VW, Ta L, Tsang JE, Higgins B, Gilmore WB, Bayley NA, Harati MD, Lee JT, Yong WH, Kornblum HI, Bensinger SJ, Mischel PS, Rao PN, Clark PM, Cloughesy TF, Letai A, Nathanson DA. Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma. Nat Med. 2017 Nov; 23(11):1342-1351.
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Weisberg EL, Schauer NJ, Yang J, Lamberto I, Doherty L, Bhatt S, Nonami A, Meng C, Letai A, Wright R, Tiv H, Gokhale PC, Ritorto MS, De Cesare V, Trost M, Christodoulou A, Christie A, Weinstock DM, Adamia S, Stone R, Chauhan D, Anderson KC, Seo HS, Dhe-Paganon S, Sattler M, Gray NS, Griffin JD, Buhrlage SJ. Inhibition of USP10 induces degradation of oncogenic FLT3. Nat Chem Biol. 2017 Dec; 13(12):1207-1215.
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Letai A. Functional precision cancer medicine-moving beyond pure genomics. Nat Med. 2017 Sep 08; 23(9):1028-1035.
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Jenson JM, Ryan JA, Grant RA, Letai A, Keating AE. Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1. Elife. 2017 06 08; 6.
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Zwang Y, Jonas O, Chen C, Rinne ML, Doench JG, Piccioni F, Tan L, Huang HT, Wang J, Ham YJ, O'Connell J, Bhola P, Doshi M, Whitman M, Cima M, Letai A, Root DE, Langer RS, Gray N, Hahn WC. Synergistic interactions with PI3K inhibition that induce apoptosis. Elife. 2017 05 31; 6.
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Price AM, Dai J, Bazot Q, Patel L, Nikitin PA, Djavadian R, Winter PS, Salinas CA, Barry AP, Wood KC, Johannsen EC, Letai A, Allday MJ, Luftig MA. Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection. Elife. 2017 04 20; 6.
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Guerriero JL, Sotayo A, Ponichtera HE, Castrillon JA, Pourzia AL, Schad S, Johnson SF, Carrasco RD, Lazo S, Bronson RT, Davis SP, Lobera M, Nolan MA, Letai A. Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature. 2017 03 16; 543(7645):428-432.
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Pallis M, Burrows F, Ryan J, Grundy M, Seedhouse C, Abdul-Aziz A, Montero J, Letai A, Russell N. Complementary dynamic BH3 profiles predict co-operativity between the multi-kinase inhibitor TG02 and the BH3 mimetic ABT-199 in acute myeloid leukaemia cells. Oncotarget. 2017 Mar 07; 8(10):16220-16232.
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Deng J, Isik E, Fernandes SM, Brown JR, Letai A, Davids MS. Bruton's tyrosine kinase inhibition increases BCL-2 dependence and enhances sensitivity to venetoclax in chronic lymphocytic leukemia. Leukemia. 2017 Oct; 31(10):2075-2084.
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Sarosiek KA, Fraser C, Muthalagu N, Bhola PD, Chang W, McBrayer SK, Cantlon A, Fisch S, Golomb-Mello G, Ryan JA, Deng J, Jian B, Corbett C, Goldenberg M, Madsen JR, Liao R, Walsh D, Sedivy J, Murphy DJ, Carrasco DR, Robinson S, Moslehi J, Letai A. Developmental Regulation of Mitochondrial Apoptosis by c-Myc Governs Age- and Tissue-Specific Sensitivity to Cancer Therapeutics. Cancer Cell. 2017 01 09; 31(1):142-156.
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Pécot J, Maillet L, Le Pen J, Vuillier C, Trécesson SC, Fétiveau A, Sarosiek KA, Bock FJ, Braun F, Letai A, Tait SWG, Gautier F, Juin PP. Tight Sequestration of BH3 Proteins by BCL-xL at Subcellular Membranes Contributes to Apoptotic Resistance. Cell Rep. 2016 12 20; 17(12):3347-3358.
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Lee T, Bian Z, Zhao B, Hogdal LJ, Sensintaffar JL, Goodwin CM, Belmar J, Shaw S, Tarr JC, Veerasamy N, Matulis SM, Koss B, Fischer MA, Arnold AL, Camper DV, Browning CF, Rossanese OW, Budhraja A, Opferman J, Boise LH, Savona MR, Letai A, Olejniczak ET, Fesik SW. Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors. FEBS Lett. 2017 Jan; 591(1):240-251.
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Montero J, Stephansky J, Cai T, Griffin GK, Cabal-Hierro L, Togami K, Hogdal LJ, Galinsky I, Morgan EA, Aster JC, Davids MS, LeBoeuf NR, Stone RM, Konopleva M, Pemmaraju N, Letai A, Lane AA. Blastic Plasmacytoid Dendritic Cell Neoplasm Is Dependent on BCL2 and Sensitive to Venetoclax. Cancer Discov. 2017 Feb; 7(2):156-164.
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Letai A. S63845, an MCL-1 Selective BH3 Mimetic: Another Arrow in Our Quiver. Cancer Cell. 2016 Dec 12; 30(6):834-835.
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Taylor-Weiner A, Zack T, O'Donnell E, Guerriero JL, Bernard B, Reddy A, Han GC, AlDubayan S, Amin-Mansour A, Schumacher SE, Litchfield K, Turnbull C, Gabriel S, Beroukhim R, Getz G, Carter SL, Hirsch MS, Letai A, Sweeney C, Van Allen EM. Genomic evolution and chemoresistance in germ-cell tumours. Nature. 2016 11 30; 540(7631):114-118.
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Potter DS, Letai A. To Prime, or Not to Prime: That Is the Question. Cold Spring Harb Symp Quant Biol. 2016; 81:131-140.
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Pham TD, Pham PQ, Li J, Letai AG, Wallace DC, Burke PJ. Cristae remodeling causes acidification detected by integrated graphene sensor during mitochondrial outer membrane permeabilization. Sci Rep. 2016 10 27; 6:35907.
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Sarosiek KA, Letai A. Directly targeting the mitochondrial pathway of apoptosis for cancer therapy using BH3 mimetics - recent successes, current challenges and future promise. FEBS J. 2016 10; 283(19):3523-3533.
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Marusyk A, Tabassum DP, Janiszewska M, Place AE, Trinh A, Rozhok AI, Pyne S, Guerriero JL, Shu S, Ekram M, Ishkin A, Cahill DP, Nikolsky Y, Chan TA, Rimawi MF, Hilsenbeck S, Schiff R, Osborne KC, Letai A, Polyak K. Spatial Proximity to Fibroblasts Impacts Molecular Features and Therapeutic Sensitivity of Breast Cancer Cells Influencing Clinical Outcomes. Cancer Res. 2016 11 15; 76(22):6495-6506.
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Bhola PD, Mar BG, Lindsley RC, Ryan JA, Hogdal LJ, Vo TT, DeAngelo DJ, Galinsky I, Ebert BL, Letai A. Functionally identifiable apoptosis-insensitive subpopulations determine chemoresistance in acute myeloid leukemia. J Clin Invest. 2016 Oct 03; 126(10):3827-3836.
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Konopleva M, Pollyea DA, Potluri J, Chyla B, Hogdal L, Busman T, McKeegan E, Salem AH, Zhu M, Ricker JL, Blum W, DiNardo CD, Kadia T, Dunbar M, Kirby R, Falotico N, Leverson J, Humerickhouse R, Mabry M, Stone R, Kantarjian H, Letai A. Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia. Cancer Discov. 2016 10; 6(10):1106-1117.
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Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, Stevenson KE, Rao P, Vadhi R, Andreeff M, Armand P, Ballen KK, Barzaghi-Rinaudo P, Cahill S, Clark RA, Cooke VG, Davids MS, DeAngelo DJ, Dorfman DM, Eaton H, Ebert BL, Etchin J, Firestone B, Fisher DC, Freedman AS, Galinsky IA, Gao H, Garcia JS, Garnache-Ottou F, Graubert TA, Gutierrez A, Halilovic E, Harris MH, Herbert ZT, Horwitz SM, Inghirami G, Intlekofer AM, Ito M, Izraeli S, Jacobsen ED, Jacobson CA, Jeay S, Jeremias I, Kelliher MA, Koch R, Konopleva M, Kopp N, Kornblau SM, Kung AL, Kupper TS, LeBoeuf NR, LaCasce AS, Lees E, Li LS, Look AT, Murakami M, Muschen M, Neuberg D, Ng SY, Odejide OO, Orkin SH, Paquette RR, Place AE, Roderick JE, Ryan JA, Sallan SE, Shoji B, Silverman LB, Soiffer RJ, Steensma DP, Stegmaier K, Stone RM, Tamburini J, Thorner AR, van Hummelen P, Wadleigh M, Wiesmann M, Weng AP, Wuerthner JU, Williams DA, Wollison BM, Lane AA, Letai A, Bertagnolli MM, Ritz J, Brown M, Long H, Aster JC, Shipp MA, Griffin JD, Weinstock DM. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 07 11; 30(1):183.
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Ryan J, Montero J, Rocco J, Letai A. iBH3: simple, fixable BH3 profiling to determine apoptotic priming in primary tissue by flow cytometry. Biol Chem. 2016 07 01; 397(7):671-8.
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Burger JA, Landau DA, Taylor-Weiner A, Bozic I, Zhang H, Sarosiek K, Wang L, Stewart C, Fan J, Hoellenriegel J, Sivina M, Dubuc AM, Fraser C, Han Y, Li S, Livak KJ, Zou L, Wan Y, Konoplev S, Sougnez C, Brown JR, Abruzzo LV, Carter SL, Keating MJ, Davids MS, Wierda WG, Cibulskis K, Zenz T, Werner L, Dal Cin P, Kharchencko P, Neuberg D, Kantarjian H, Lander E, Gabriel S, O'Brien S, Letai A, Weitz DA, Nowak MA, Getz G, Wu CJ. Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition. Nat Commun. 2016 May 20; 7:11589.
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Brem EA, Letai A. BOK: Oddball of the BCL-2 Family. Trends Cell Biol. 2016 06; 26(6):389-390.
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Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, Stevenson KE, Rao P, Vadhi R, Andreeff M, Armand P, Ballen KK, Barzaghi-Rinaudo P, Cahill S, Clark RA, Cooke VG, Davids MS, DeAngelo DJ, Dorfman DM, Eaton H, Ebert BL, Etchin J, Firestone B, Fisher DC, Freedman AS, Galinsky IA, Gao H, Garcia JS, Garnache-Ottou F, Graubert TA, Gutierrez A, Halilovic E, Harris MH, Herbert ZT, Horwitz SM, Inghirami G, Intlekofer AM, Ito M, Izraeli S, Jacobsen ED, Jacobson CA, Jeay S, Jeremias I, Kelliher MA, Koch R, Konopleva M, Kopp N, Kornblau SM, Kung AL, Kupper TS, LeBoeuf NR, LaCasce AS, Lees E, Li LS, Look AT, Murakami M, Muschen M, Neuberg D, Ng SY, Odejide OO, Orkin SH, Paquette RR, Place AE, Roderick JE, Ryan JA, Sallan SE, Shoji B, Silverman LB, Soiffer RJ, Steensma DP, Stegmaier K, Stone RM, Tamburini J, Thorner AR, van Hummelen P, Wadleigh M, Wiesmann M, Weng AP, Wuerthner JU, Williams DA, Wollison BM, Lane AA, Letai A, Bertagnolli MM, Ritz J, Brown M, Long H, Aster JC, Shipp MA, Griffin JD, Weinstock DM. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 04 11; 29(4):574-586.
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Anderson MA, Deng J, Seymour JF, Tam C, Kim SY, Fein J, Yu L, Brown JR, Westerman D, Si EG, Majewski IJ, Segal D, Heitner Enschede SL, Huang DC, Davids MS, Letai A, Roberts AW. The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism. Blood. 2016 06 23; 127(25):3215-24.
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Montero J, Letai A. Dynamic BH3 profiling-poking cancer cells with a stick. Mol Cell Oncol. 2016 May; 3(3):e1040144.
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Koss B, Ryan J, Budhraja A, Szarama K, Yang X, Bathina M, Cardone MH, Nikolovska-Coleska Z, Letai A, Opferman JT. Defining specificity and on-target activity of BH3-mimetics using engineered B-ALL cell lines. Oncotarget. 2016 Mar 08; 7(10):11500-11.
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Bhola PD, Letai A. Mitochondria-Judges and Executioners of Cell Death Sentences. Mol Cell. 2016 Mar 03; 61(5):695-704.
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Rezaei Araghi R, Ryan JA, Letai A, Keating AE. Rapid Optimization of Mcl-1 Inhibitors using Stapled Peptide Libraries Including Non-Natural Side Chains. ACS Chem Biol. 2016 05 20; 11(5):1238-44.
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Benito JM, Godfrey L, Kojima K, Hogdal L, Wunderlich M, Geng H, Marzo I, Harutyunyan KG, Golfman L, North P, Kerry J, Ballabio E, Chonghaile TN, Gonzalo O, Qiu Y, Jeremias I, Debose L, O'Brien E, Ma H, Zhou P, Jacamo R, Park E, Coombes KR, Zhang N, Thomas DA, O'Brien S, Kantarjian HM, Leverson JD, Kornblau SM, Andreeff M, Müschen M, Zweidler-McKay PA, Mulloy JC, Letai A, Milne TA, Konopleva M. MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199. Cell Rep. 2015 Dec 29; 13(12):2715-27.
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Letai A. Cell Death and Cancer Therapy: Don't Forget to Kill the Cancer Cell! Clin Cancer Res. 2015 Nov 15; 21(22):5015-20.
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Friedman AA, Letai A, Fisher DE, Flaherty KT. Precision medicine for cancer with next-generation functional diagnostics. Nat Rev Cancer. 2015 Dec; 15(12):747-56.
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Etchin J, Montero J, Berezovskaya A, Le BT, Kentsis A, Christie AL, Conway AS, Chen WC, Reed C, Mansour MR, Ng CE, Adamia S, Rodig SJ, Galinsky IA, Stone RM, Klebanov B, Landesman Y, Kauffman M, Shacham S, Kung AL, Wang JC, Letai A, Look AT. Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice. Leukemia. 2016 Jan; 30(1):190-9.
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Bhatt S, Matthews J, Parvin S, Sarosiek KA, Zhao D, Jiang X, Isik E, Letai A, Lossos IS. Direct and immune-mediated cytotoxicity of interleukin-21 contributes to antitumor effects in mantle cell lymphoma. Blood. 2015 Sep 24; 126(13):1555-64.
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Touzeau C, Ryan J, Guerriero J, Moreau P, Chonghaile TN, Le Gouill S, Richardson P, Anderson K, Amiot M, Letai A. BH3 profiling identifies heterogeneous dependency on Bcl-2 family members in multiple myeloma and predicts sensitivity to BH3 mimetics. Leukemia. 2016 Mar; 30(3):761-4.
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Wu SC, Li LS, Kopp N, Montero J, Chapuy B, Yoda A, Christie AL, Liu H, Christodoulou A, van Bodegom D, van der Zwet J, Layer JV, Tivey T, Lane AA, Ryan JA, Ng SY, DeAngelo DJ, Stone RM, Steensma D, Wadleigh M, Harris M, Mandon E, Ebel N, Andraos R, Romanet V, Dölemeyer A, Sterker D, Zender M, Rodig SJ, Murakami M, Hofmann F, Kuo F, Eck MJ, Silverman LB, Sallan SE, Letai A, Baffert F, Vangrevelinghe E, Radimerski T, Gaul C, Weinstock DM. Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia. Cancer Cell. 2015 Jul 13; 28(1):29-41.
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Montero J, Sarosiek KA, DeAngelo JD, Maertens O, Ryan J, Ercan D, Piao H, Horowitz NS, Berkowitz RS, Matulonis U, Jänne PA, Amrein PC, Cichowski K, Drapkin R, Letai A. Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy. Cell. 2015 Feb 26; 160(5):977-989.
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Winter PS, Sarosiek KA, Lin KH, Meggendorfer M, Schnittger S, Letai A, Wood KC. RAS signaling promotes resistance to JAK inhibitors by suppressing BAD-mediated apoptosis. Sci Signal. 2014 Dec 23; 7(357):ra122.
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Dutta S, Ryan J, Chen TS, Kougentakis C, Letai A, Keating AE. Potent and specific peptide inhibitors of human pro-survival protein Bcl-xL. J Mol Biol. 2015 Mar 27; 427(6 Pt B):1241-1253.
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Bah N, Maillet L, Ryan J, Dubreil S, Gautier F, Letai A, Juin P, Barillé-Nion S. Bcl-xL controls a switch between cell death modes during mitotic arrest. Cell Death Dis. 2014; 5:e1429.
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Foight GW, Ryan JA, Gullá SV, Letai A, Keating AE. Designed BH3 peptides with high affinity and specificity for targeting Mcl-1 in cells. ACS Chem Biol. 2014 Sep 19; 9(9):1962-8.
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Suryani S, Carol H, Chonghaile TN, Frismantas V, Sarmah C, High L, Bornhauser B, Cowley MJ, Szymanska B, Evans K, Boehm I, Tonna E, Jones L, Manesh DM, Kurmasheva RT, Billups C, Kaplan W, Letai A, Bourquin JP, Houghton PJ, Smith MA, Lock RB. Cell and molecular determinants of in vivo efficacy of the BH3 mimetic ABT-263 against pediatric acute lymphoblastic leukemia xenografts. Clin Cancer Res. 2014 Sep 01; 20(17):4520-31.
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Chonghaile TN, Roderick JE, Glenfield C, Ryan J, Sallan SE, Silverman LB, Loh ML, Hunger SP, Wood B, DeAngelo DJ, Stone R, Harris M, Gutierrez A, Kelliher MA, Letai A. Maturation stage of T-cell acute lymphoblastic leukemia determines BCL-2 versus BCL-XL dependence and sensitivity to ABT-199. Cancer Discov. 2014 Sep; 4(9):1074-87.
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Bah N, Maillet L, Ryan J, Dubreil S, Gautier F, Letai A, Juin P, Barillé-Nion S. Bcl-xL controls a switch between cell death modes during mitotic arrest. Cell Death Dis. 2014 Jun 12; 5:e1291.
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Wan L, Tan M, Yang J, Inuzuka H, Dai X, Wu T, Liu J, Shaik S, Chen G, Deng J, Malumbres M, Letai A, Kirschner MW, Sun Y, Wei W. APC(Cdc20) suppresses apoptosis through targeting Bim for ubiquitination and destruction. Dev Cell. 2014 May 27; 29(4):377-91.
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Murase K, Kim HT, Bascug OR, Kawano Y, Ryan J, Matsuoka K, Davids MS, Koreth J, Ho VT, Cutler C, Armand P, Alyea EP, Blazar BR, Antin JH, Soiffer RJ, Letai A, Ritz J. Increased mitochondrial apoptotic priming of human regulatory T cells after allogeneic hematopoietic stem cell transplantation. Haematologica. 2014 Sep; 99(9):1499-508.
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Murphy ÁC, Weyhenmeyer B, Noonan J, Kilbride SM, Schimansky S, Loh KP, Kögel D, Letai AG, Prehn JH, Murphy BM. Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis. Apoptosis. 2014 Apr; 19(4):629-42.
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Colak S, Zimberlin CD, Fessler E, Hogdal L, Prasetyanti PR, Grandela CM, Letai A, Medema JP. Decreased mitochondrial priming determines chemoresistance of colon cancer stem cells. Cell Death Differ. 2014 Jul; 21(7):1170-7.
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Hata AN, Yeo A, Faber AC, Lifshits E, Chen Z, Cheng KA, Walton Z, Sarosiek KA, Letai A, Heist RS, Mino-Kenudson M, Wong KK, Engelman JA. Failure to induce apoptosis via BCL-2 family proteins underlies lack of efficacy of combined MEK and PI3K inhibitors for KRAS-mutant lung cancers. Cancer Res. 2014 Jun 01; 74(11):3146-56.
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Pan R, Hogdal LJ, Benito JM, Bucci D, Han L, Borthakur G, Cortes J, DeAngelo DJ, Debose L, Mu H, Döhner H, Gaidzik VI, Galinsky I, Golfman LS, Haferlach T, Harutyunyan KG, Hu J, Leverson JD, Marcucci G, Müschen M, Newman R, Park E, Ruvolo PP, Ruvolo V, Ryan J, Schindela S, Zweidler-McKay P, Stone RM, Kantarjian H, Andreeff M, Konopleva M, Letai AG. Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia. Cancer Discov. 2014 Mar; 4(3):362-75.
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Sarosiek KA, Chi X, Bachman JA, Sims JJ, Montero J, Patel L, Flanagan A, Andrews DW, Sorger P, Letai A. BID preferentially activates BAK while BIM preferentially activates BAX, affecting chemotherapy response. Mol Cell. 2013 Sep 26; 51(6):751-65.
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Sarosiek KA, Ni Chonghaile T, Letai A. Mitochondria: gatekeepers of response to chemotherapy. Trends Cell Biol. 2013 Dec; 23(12):612-9.
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Liu JC, Guan X, Ryan JA, Rivera AG, Mock C, Agrawal V, Agarwal V, Letai A, Lerou PH, Lahav G. High mitochondrial priming sensitizes hESCs to DNA-damage-induced apoptosis. Cell Stem Cell. 2013 Oct 03; 13(4):483-91.
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Davids MS, Letai A, Brown JR. Overcoming stroma-mediated treatment resistance in chronic lymphocytic leukemia through BCL-2 inhibition. Leuk Lymphoma. 2013 Aug; 54(8):1823-5.
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Montero J, Dutta C, van Bodegom D, Weinstock D, Letai A. p53 regulates a non-apoptotic death induced by ROS. Cell Death Differ. 2013 Nov; 20(11):1465-74.
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Ryan J, Letai A. BH3 profiling in whole cells by fluorimeter or FACS. Methods. 2013 Jun 01; 61(2):156-64.
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Hogdal LJ, Letai A. BCL-2 inhibition: stemming the tide of myeloid malignancies. Cell Stem Cell. 2013 Mar 07; 12(3):269-70.
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Davids MS, Letai A. ABT-199: taking dead aim at BCL-2. Cancer Cell. 2013 Feb 11; 23(2):139-41.
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Etchin J, Sanda T, Mansour MR, Kentsis A, Montero J, Le BT, Christie AL, McCauley D, Rodig SJ, Kauffman M, Shacham S, Stone R, Letai A, Kung AL, Thomas Look A. KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia. Br J Haematol. 2013 Apr; 161(1):117-27.
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Deng J, Letai A. Priming BCL-2 to kill: the combination therapy of tamoxifen and ABT-199 in ER+ breast cancer. Breast Cancer Res. 2013; 15(5):317.
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Vo TT, Ryan J, Carrasco R, Neuberg D, Rossi DJ, Stone RM, Deangelo DJ, Frattini MG, Letai A. Relative mitochondrial priming of myeloblasts and normal HSCs determines chemotherapeutic success in AML. Cell. 2012 Oct 12; 151(2):344-55.
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Ercan D, Xu C, Yanagita M, Monast CS, Pratilas CA, Montero J, Butaney M, Shimamura T, Sholl L, Ivanova EV, Tadi M, Rogers A, Repellin C, Capelletti M, Maertens O, Goetz EM, Letai A, Garraway LA, Lazzara MJ, Rosen N, Gray NS, Wong KK, Jänne PA. Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors. Cancer Discov. 2012 Oct; 2(10):934-47.
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Davids MS, Deng J, Wiestner A, Lannutti BJ, Wang L, Wu CJ, Wilson WH, Brown JR, Letai A. Decreased mitochondrial apoptotic priming underlies stroma-mediated treatment resistance in chronic lymphocytic leukemia. Blood. 2012 Oct 25; 120(17):3501-9.
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Dutta C, Day T, Kopp N, van Bodegom D, Davids MS, Ryan J, Bird L, Kommajosyula N, Weigert O, Yoda A, Fung H, Brown JR, Shapiro GI, Letai A, Weinstock DM. BCL2 suppresses PARP1 function and nonapoptotic cell death. Cancer Res. 2012 Aug 15; 72(16):4193-203.
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Davids MS, Letai A. Targeting the B-cell lymphoma/leukemia 2 family in cancer. J Clin Oncol. 2012 Sep 01; 30(25):3127-35.
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Rodriguez DA, Zamorano S, Lisbona F, Rojas-Rivera D, Urra H, Cubillos-Ruiz JR, Armisen R, Henriquez DR, Cheng EH, Letek M, Vaisar T, Irrazabal T, Gonzalez-Billault C, Letai A, Pimentel-Muiños FX, Kroemer G, Hetz C. BH3-only proteins are part of a regulatory network that control the sustained signalling of the unfolded protein response sensor IRE1a. EMBO J. 2012 May 16; 31(10):2322-35.
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Del Gaizo Moore V, Letai A. BH3 profiling--measuring integrated function of the mitochondrial apoptotic pathway to predict cell fate decisions. Cancer Lett. 2013 May 28; 332(2):202-5.
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Ni Chonghaile T, Letai A. Who put the "A" in Atg12: autophagy or apoptosis? Mol Cell. 2011 Dec 23; 44(6):844-5.
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Azab AK, Quang P, Azab F, Pitsillides C, Thompson B, Chonghaile T, Patton JT, Maiso P, Monrose V, Sacco A, Ngo HT, Flores LM, Lin CP, Magnani JL, Kung AL, Letai A, Carrasco R, Roccaro AM, Ghobrial IM. P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment. Blood. 2012 Feb 09; 119(6):1468-78.
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Ni Chonghaile T, Sarosiek KA, Vo TT, Ryan JA, Tammareddi A, Moore Vdel G, Deng J, Anderson KC, Richardson P, Tai YT, Mitsiades CS, Matulonis UA, Drapkin R, Stone R, Deangelo DJ, McConkey DJ, Sallan SE, Silverman L, Hirsch MS, Carrasco DR, Letai A. Pretreatment mitochondrial priming correlates with clinical response to cytotoxic chemotherapy. Science. 2011 Nov 25; 334(6059):1129-33.
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Letai A. Targeting Bcl-2 in CLL: cui bono? Blood. 2011 Sep 29; 118(13):3453-4.
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Barbone D, Ryan JA, Kolhatkar N, Chacko AD, Jablons DM, Sugarbaker DJ, Bueno R, Letai AG, Coussens LM, Fennell DA, Broaddus VC. The Bcl-2 repertoire of mesothelioma spheroids underlies acquired apoptotic multicellular resistance. Cell Death Dis. 2011 Jun 23; 2:e174.
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Letai A. A new face of BCL-2 inhibition in CLL. Blood. 2011 Mar 10; 117(10):2750-1.
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Ryan JA, Brunelle JK, Letai A. Heightened mitochondrial priming is the basis for apoptotic hypersensitivity of CD4+ CD8+ thymocytes. Proc Natl Acad Sci U S A. 2010 Jul 20; 107(29):12895-900.
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Kutuk O, Letai A. Displacement of Bim by Bmf and Puma rather than increase in Bim level mediates paclitaxel-induced apoptosis in breast cancer cells. Cell Death Differ. 2010 Oct; 17(10):1624-35.
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Yecies D, Carlson NE, Deng J, Letai A. Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1. Blood. 2010 Apr 22; 115(16):3304-13.
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Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga J, Tsao MS, Demichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson M. The landscape of somatic copy-number alteration across human cancers. Nature. 2010 Feb 18; 463(7283):899-905.
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Vo TT, Letai A. BH3-only proteins and their effects on cancer. Adv Exp Med Biol. 2010; 687:49-63.
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Brunelle JK, Ryan J, Yecies D, Opferman JT, Letai A. MCL-1-dependent leukemia cells are more sensitive to chemotherapy than BCL-2-dependent counterparts. J Cell Biol. 2009 Nov 02; 187(3):429-42.
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Berger AK, Cortese GP, Amodeo KD, Weihofen A, Letai A, LaVoie MJ. Parkin selectively alters the intrinsic threshold for mitochondrial cytochrome c release. Hum Mol Genet. 2009 Nov 15; 18(22):4317-28.
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Dutta-Simmons J, Zhang Y, Gorgun G, Gatt M, Mani M, Hideshima T, Takada K, Carlson NE, Carrasco DE, Tai YT, Raje N, Letai AG, Anderson KC, Carrasco DR. Aurora kinase A is a target of Wnt/beta-catenin involved in multiple myeloma disease progression. Blood. 2009 Sep 24; 114(13):2699-708.
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Letai A. Hiding from ABT-737 in lymph nodes. Blood. 2009 Apr 30; 113(18):4132-3.
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Letai A. Puma strikes Bax. J Cell Biol. 2009 Apr 20; 185(2):189-91.
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Brunelle JK, Letai A. Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci. 2009 Feb 15; 122(Pt 4):437-41.
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Ni Chonghaile T, Letai A. Mimicking the BH3 domain to kill cancer cells. Oncogene. 2008 Dec; 27 Suppl 1:S149-57.
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Kutuk O, Letai A. Alteration of the mitochondrial apoptotic pathway is key to acquired paclitaxel resistance and can be reversed by ABT-737. Cancer Res. 2008 Oct 01; 68(19):7985-94.
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Jette CA, Flanagan AM, Ryan J, Pyati UJ, Carbonneau S, Stewart RA, Langenau DM, Look AT, Letai A. BIM and other BCL-2 family proteins exhibit cross-species conservation of function between zebrafish and mammals. Cell Death Differ. 2008 Jun; 15(6):1063-72.
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Kutuk O, Letai A. Regulation of Bcl-2 family proteins by posttranslational modifications. Curr Mol Med. 2008 Mar; 8(2):102-18.
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Letai AG. Diagnosing and exploiting cancer's addiction to blocks in apoptosis. Nat Rev Cancer. 2008 Feb; 8(2):121-32.
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Anthony Letai and Victoria Del Gaizo Moore. Apoptosis Dysregulation in CLL. Chronic Lymphocytic Leukemia. 2008.
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Del Gaizo Moore V, Letai A. Rational design of therapeutics targeting the BCL-2 family: are some cancer cells primed for death but waiting for a final push? Adv Exp Med Biol. 2008; 615:159-75.
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Del Gaizo Moore VD, Letai A. Rational design of therapeutics targeting the BCL-2 famil: Are some cancer cells primed for death but waiting for a final push?. Programmed Cell Death in Cancer Progression and Therapy. 2008; 159-176.
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Deng J, Shimamura T, Perera S, Carlson NE, Cai D, Shapiro GI, Wong KK, Letai A. Proapoptotic BH3-only BCL-2 family protein BIM connects death signaling from epidermal growth factor receptor inhibition to the mitochondrion. Cancer Res. 2007 Dec 15; 67(24):11867-75.
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Flanagan AM, Letai A. BH3 domains define selective inhibitory interactions with BHRF-1 and KSHV BCL-2. Cell Death Differ. 2008 Mar; 15(3):580-8.
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Del Gaizo Moore V, Schlis KD, Sallan SE, Armstrong SA, Letai A. BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia. Blood. 2008 Feb 15; 111(4):2300-9.
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Deng J, Carlson N, Takeyama K, Dal Cin P, Shipp M, Letai A. BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell. 2007 Aug; 12(2):171-85.
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Del Gaizo Moore V, Brown JR, Certo M, Love TM, Novina CD, Letai A. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest. 2007 Jan; 117(1):112-21.
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Letai A. Restoring cancer's death sentence. Cancer Cell. 2006 Nov; 10(5):343-5.
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Letai A, Scorrano L. Laying the foundations of programmed cell death. Cell Death Differ. 2006 Aug; 13(8):1245-7.
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Certo M, Del Gaizo Moore V, Nishino M, Wei G, Korsmeyer S, Armstrong SA, Letai A. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell. 2006 May; 9(5):351-65.
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Goldsmith KC, Liu X, Dam V, Morgan BT, Shabbout M, Cnaan A, Letai A, Korsmeyer SJ, Hogarty MD. BH3 peptidomimetics potently activate apoptosis and demonstrate single agent efficacy in neuroblastoma. Oncogene. 2006 Aug 03; 25(33):4525-33.
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Letai A. Growth factor withdrawal and apoptosis: the middle game. Mol Cell. 2006 Mar 17; 21(6):728-30.
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Chauhan D, Catley L, Li G, Podar K, Hideshima T, Velankar M, Mitsiades C, Mitsiades N, Yasui H, Letai A, Ovaa H, Berkers C, Nicholson B, Chao TH, Neuteboom ST, Richardson P, Palladino MA, Anderson KC. A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell. 2005 Nov; 8(5):407-19.
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Letai A. Pharmacological manipulation of Bcl-2 family members to control cell death. J Clin Invest. 2005 Oct; 115(10):2648-55.
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Letai A. BCL-2: found bound and drugged! Trends Mol Med. 2005 Oct; 11(10):442-4.
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Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer SJ, Kunzer AR, Letai A, Li C, Mitten MJ, Nettesheim DG, Ng S, Nimmer PM, O'Connor JM, Oleksijew A, Petros AM, Reed JC, Shen W, Tahir SK, Thompson CB, Tomaselli KJ, Wang B, Wendt MD, Zhang H, Fesik SW, Rosenberg SH. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005 Jun 02; 435(7042):677-81.
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Anthony G. Letai John G. Gribben. Lymphoid Neoplasms. Molecular Hematology. 2005; 105-114.
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Letai A, Sorcinelli MD, Beard C, Korsmeyer SJ. Antiapoptotic BCL-2 is required for maintenance of a model leukemia. Cancer Cell. 2004 Sep; 6(3):241-9.
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Opferman JT, Letai A, Beard C, Sorcinelli MD, Ong CC, Korsmeyer SJ. Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature. 2003 Dec 11; 426(6967):671-6.
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Letai AG. Smallpox and smallpox vaccination. N Engl J Med. 2003 May 08; 348(19):1920-5; author reply 1920-5.
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Letai A. BH3 domains as BCL-2 inhibitors: prototype cancer therapeutics. Expert Opin Biol Ther. 2003 Apr; 3(2):293-304.
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Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell. 2002 Sep; 2(3):183-92.
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Letai A, Kuter DJ. Cancer, coagulation, and anticoagulation. Oncologist. 1999; 4(6):443-9.
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Letai A, Fuchs E. The importance of intramolecular ion pairing in intermediate filaments. Proc Natl Acad Sci U S A. 1995 Jan 03; 92(1):92-6.
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Fuchs E, Coulombe P, Cheng J, Chan YM, Hutton E, Syder A, Degenstein L, Yu QC, Letai A, Vassar R. Genetic bases of epidermolysis bullosa simplex and epidermolytic hyperkeratosis. J Invest Dermatol. 1994 Nov; 103(5 Suppl):25S-30S.
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Letai A, Coulombe PA, McCormick MB, Yu QC, Hutton E, Fuchs E. Disease severity correlates with position of keratin point mutations in patients with epidermolysis bullosa simplex. Proc Natl Acad Sci U S A. 1993 Apr 15; 90(8):3197-201.
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Anthony Letai. Keratin Mutations and Heritable Skin Disease. 1993.
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Cheng J, Syder AJ, Yu QC, Letai A, Paller AS, Fuchs E. The genetic basis of epidermolytic hyperkeratosis: a disorder of differentiation-specific epidermal keratin genes. Cell. 1992 Sep 04; 70(5):811-9.
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Letai A, Coulombe PA, Fuchs E. Do the ends justify the mean? Proline mutations at the ends of the keratin coiled-coil rod segment are more disruptive than internal mutations. J Cell Biol. 1992 Mar; 116(5):1181-95.
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Coulombe PA, Hutton ME, Letai A, Hebert A, Paller AS, Fuchs E. Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: genetic and functional analyses. Cell. 1991 Sep 20; 66(6):1301-11.
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Lloyd DM, Cotler SJ, Letai AG, Stuart FP, Thistlethwaite JR. Pancreas-graft immunogenicity and pretreatment with anti-class II monoclonal antibodies. Diabetes. 1989 Jan; 38 Suppl 1:104-8.
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Letai AG, Palladino MA, Fromm E, Rizzo V, Fresco JR. Specificity in formation of triple-stranded nucleic acid helical complexes: studies with agarose-linked polyribonucleotide affinity columns. Biochemistry. 1988 Dec 27; 27(26):9108-12.
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