Anthony G. Letai, MD, PhD

Anthony G. Letai, MD, PhD

Medical Oncology

Contact Information

Office Phone Number

617-632-2348

Fax

617-582-8160

Appointments

617-632-6140

Biography

Anthony G. Letai, MD, PhD

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.

Researcher

Physician

Physician
Professor of Medicine, Harvard Medical School

Centers/Programs

Clinical Interests

Leukemias

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.

    Publications

      • The Siren Song of Synergy. Blood Cancer Discov. 2024 Feb 08; OF1-OF2. View in: Pubmed

      • Prophylactic maintenance with venetoclax/azacitidine after reduced intensity conditioning allo-transplant for high risk MDS and AML. Blood Adv. 2024 Jan 10. View in: Pubmed

      • Heterogeneity and transcriptional drivers of triple-negative breast cancer. Cell Rep. 2023 12 26; 42(12):113564. View in: Pubmed

      • BH3 profiling as pharmacodynamic biomarker for the activity of BH3 mimetics. Haematologica. 2023 Oct 26. View in: Pubmed

      • Targeting conditioned media dependencies and FLT-3 in chronic lymphocytic leukemia. Blood Adv. 2023 10 10; 7(19):5877-5889. View in: Pubmed

      • BH3 profiling identifies BCL-2 dependence in adult patients with early T-cell progenitor acute lymphoblastic leukemia. Blood Adv. 2023 06 27; 7(12):2917-2923. View in: Pubmed

      • Sequential apoptotic and multiplexed proteomic evaluation of single cancer cells. Sci Adv. 2023 06 23; 9(25):eadg4128. View in: Pubmed

      • Dynamic BH3 profiling identifies pro-apoptotic drug combinations for the treatment of malignant pleural mesothelioma. Nat Commun. 2023 05 20; 14(1):2897. View in: Pubmed

      • Quantifying requirements for mitochondrial apoptosis in CAR T killing of cancer cells. Cell Death Dis. 2023 04 13; 14(4):267. View in: Pubmed

      • Lisaftoclax (APG-2575) Is a Novel BCL-2 Inhibitor with Robust Antitumor Activity in Preclinical Models of Hematologic Malignancy. Clin Cancer Res. 2022 12 15; 28(24):5455-5468. View in: Pubmed

      • Collateral deletion of the mitochondrial AAA+ ATPase ATAD1 sensitizes cancer cells to proteasome dysfunction. Elife. 2022 11 21; 11. View in: Pubmed

      • Precision medicine in AML: Function plus -omics is better than either alone. Cancer Cell. 2022 08 08; 40(8):804-806. View in: Pubmed

      • Challenges and opportunities for physician-scientists in advancing cancer research. Trends Cancer. 2022 08; 8(8):615-619. View in: Pubmed

      • Author Correction: Combination therapy targeting Erk1/2 and CDK4/6i in relapsed refractory multiple myeloma. Leukemia. 2022 Jun; 36(6):1700. View in: Pubmed

      • Preclinical Modeling of Leiomyosarcoma Identifies Susceptibility to Transcriptional CDK Inhibitors through Antagonism of E2F-Driven Oncogenic Gene Expression. Clin Cancer Res. 2022 06 01; 28(11):2397-2408. View in: Pubmed

      • IKAROS and MENIN coordinate therapeutically actionable leukemogenic gene expression in MLL-r acute myeloid leukemia. Nat Cancer. 2022 05; 3(5):595-613. View in: Pubmed

      • Augmenting NK cell-based immunotherapy by targeting mitochondrial apoptosis. Cell. 2022 04 28; 185(9):1521-1538.e18. View in: Pubmed

      • JAK3 mutations and mitochondrial apoptosis resistance in T-cell acute lymphoblastic leukemia. Leukemia. 2022 06; 36(6):1499-1507. View in: Pubmed

      • Correction: Activation of RAS/MAPK pathway confers MCL-1 mediated acquired resistance to BCL-2 inhibitor venetoclax in acute myeloid leukemia. Signal Transduct Target Ther. 2022 Apr 01; 7(1):110. View in: Pubmed

      • Apoptosis: Directly Targeted at Last. J Clin Oncol. 2022 05 20; 40(15):1693-1695. View in: Pubmed

      • Activation of RAS/MAPK pathway confers MCL-1 mediated acquired resistance to BCL-2 inhibitor venetoclax in acute myeloid leukemia. Signal Transduct Target Ther. 2022 02 21; 7(1):51. View in: Pubmed

      • Functional Precision Medicine: Putting Drugs on Patient Cancer Cells and Seeing What Happens. Cancer Discov. 2022 02; 12(2):290-292. View in: Pubmed

      • Combination therapy targeting Erk1/2 and CDK4/6i in relapsed refractory multiple myeloma. Leukemia. 2022 04; 36(4):1088-1101. View in: Pubmed

      • Adding venetoclax to fludarabine/busulfan RIC transplant for high-risk MDS and AML is feasible, safe, and active. Blood Adv. 2021 12 28; 5(24):5536-5545. View in: Pubmed

      • Functional precision oncology: Testing tumors with drugs to identify vulnerabilities and novel combinations. Cancer Cell. 2022 01 10; 40(1):26-35. View in: Pubmed

      • Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1. Sci Adv. 2021 Nov 12; 7(46):eabe5469. View in: Pubmed

      • In Conversation with Tony Letai. FEBS J. 2021 11; 288(21):6087-6094. View in: Pubmed

      • Activation of Notch and Myc Signaling via B-cell-Restricted Depletion of Dnmt3a Generates a Consistent Murine Model of Chronic Lymphocytic Leukemia. Cancer Res. 2021 12 15; 81(24):6117-6130. View in: Pubmed

      • An In Vivo CRISPR Screening Platform for Prioritizing Therapeutic Targets in AML. Cancer Discov. 2022 02; 12(2):432-449. View in: Pubmed

      • BH3-only proteins are part of a regulatory network that control the sustained signalling of the unfolded protein response sensor IRE1a. EMBO J. 2021 Sep 15; 40(18):e109146. View in: Pubmed

      • Comparing syngeneic and autochthonous models of breast cancer to identify tumor immune components that correlate with response to immunotherapy in breast cancer. Breast Cancer Res. 2021 08 05; 23(1):83. View in: Pubmed

      • Dynamic BH3 profiling identifies active BH3 mimetic combinations in non-small cell lung cancer. Cell Death Dis. 2021 07 27; 12(8):741. View in: Pubmed

      • Cell Line-Specific Network Models of ER+ Breast Cancer Identify Potential PI3Ka Inhibitor Resistance Mechanisms and Drug Combinations. Cancer Res. 2021 09 01; 81(17):4603-4617. View in: Pubmed

      • Multifunctional barcoding with ClonMapper enables high-resolution study of clonal dynamics during tumor evolution and treatment. Nat Cancer. 2021 07; 2(7):758-772. View in: Pubmed

      • ER+ Breast Cancer Strongly Depends on MCL-1 and BCL-xL Anti-Apoptotic Proteins. Cells. 2021 07 02; 10(7). View in: Pubmed

      • Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening. Cancer Discov. 2021 10; 11(10):2544-2563. View in: Pubmed

      • Death in the Fas, ELANE. Cell. 2021 06 10; 184(12):3081-3083. View in: Pubmed

      • Metabolic perturbations sensitize triple-negative breast cancers to apoptosis induced by BH3 mimetics. Sci Signal. 2021 06 08; 14(686). View in: Pubmed

      • Mitochondrial apoptotic priming is a key determinant of cell fate upon p53 restoration. Proc Natl Acad Sci U S A. 2021 06 08; 118(23). View in: Pubmed

      • Comprehensive CRISPR-Cas9 screens identify genetic determinants of drug responsiveness in multiple myeloma. Blood Adv. 2021 05 11; 5(9):2391-2402. View in: Pubmed

      • Apoptotic Blocks in Primary Non-Hodgkin B Cell Lymphomas Identified by BH3 Profiling. Cancers (Basel). 2021 Feb 28; 13(5). View in: Pubmed

      • Multiple screening approaches reveal HDAC6 as a novel regulator of glycolytic metabolism in triple-negative breast cancer. Sci Adv. 2021 01; 7(3). View in: Pubmed

      • An Autochthonous Mouse Model of Myd88- and BCL2-Driven Diffuse Large B-cell Lymphoma Reveals Actionable Molecular Vulnerabilities. Blood Cancer Discov. 2021 01; 2(1):70-91. View in: Pubmed

      • Navitoclax enhances the effectiveness of EGFR-targeted antibody-drug conjugates in PDX models of EGFR-expressing triple-negative breast cancer. Breast Cancer Res. 2020 11 30; 22(1):132. View in: Pubmed

      • Reduced Mitochondrial Apoptotic Priming Drives Resistance to BH3 Mimetics in Acute Myeloid Leukemia. Cancer Cell. 2020 12 14; 38(6):872-890.e6. View in: Pubmed

      • Aneuploidy increases resistance to chemotherapeutics by antagonizing cell division. Proc Natl Acad Sci U S A. 2020 12 01; 117(48):30566-30576. View in: Pubmed

      • Venetoclax with azacitidine or decitabine in patients with newly diagnosed acute myeloid leukemia: Long term follow-up from a phase 1b study. Am J Hematol. 2021 02 01; 96(2):208-217. View in: Pubmed

      • CDK4/6 inhibition reprograms the breast cancer enhancer landscape by stimulating AP-1 transcriptional activity. Nat Cancer. 2021 01; 2(1):34-48. View in: Pubmed

      • Combined EZH2 and Bcl-2 inhibitors as precision therapy for genetically defined DLBCL subtypes. Blood Adv. 2020 10 27; 4(20):5226-5231. View in: Pubmed

      • Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 08 13; 383(7):617-629. View in: Pubmed

      • Leukemia Cell of Origin Influences Apoptotic Priming and Sensitivity to LSD1 Inhibition. Cancer Discov. 2020 10; 10(10):1500-1513. View in: Pubmed

      • High-throughput dynamic BH3 profiling may quickly and accurately predict effective therapies in solid tumors. Sci Signal. 2020 06 16; 13(636). View in: Pubmed

      • Increased mitochondrial apoptotic priming with targeted therapy predicts clinical response to re-induction chemotherapy. Am J Hematol. 2020 03; 95(3):245-250. View in: Pubmed

      • Destabilization of NOXA mRNA as a common resistance mechanism to targeted therapies. Nat Commun. 2019 11 14; 10(1):5157. View in: Pubmed

      • DNA methyltransferase inhibition overcomes diphthamide pathway deficiencies underlying CD123-targeted treatment resistance. J Clin Invest. 2019 11 01; 129(11):5005-5019. View in: Pubmed

      • Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies. Cancer Cell. 2019 10 14; 36(4):369-384.e13. View in: Pubmed

      • Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer. Mol Cancer Res. 2019 11; 17(11):2281-2293. View in: Pubmed

      • Prohibitin is a prognostic marker and therapeutic target to block chemotherapy resistance in Wilms' tumor. JCI Insight. 2019 08 08; 4(15). View in: Pubmed

      • MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer. Nat Commun. 2019 08 02; 10(1):3485. View in: Pubmed

      • Prediction of venetoclax activity in precursor B-ALL by functional assessment of apoptosis signaling. Cell Death Dis. 2019 07 29; 10(8):571. View in: Pubmed

      • BH3 profiling discriminates on-target small molecule BH3 mimetics from putative mimetics. Cell Death Differ. 2020 03; 27(3):999-1007. View in: Pubmed

      • Patterns of substrate affinity, competition, and degradation kinetics underlie biological activity of thalidomide analogs. Blood. 2019 07 11; 134(2):160-170. View in: Pubmed

      • Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol. 2019 03; 20(3):175-193. View in: Pubmed

      • MCL1 and DEDD Promote Urothelial Carcinoma Progression. Mol Cancer Res. 2019 06; 17(6):1294-1304. View in: Pubmed

      • Biomarker-driven strategy for MCL1 inhibition in T-cell lymphomas. Blood. 2019 02 07; 133(6):566-575. View in: Pubmed

      • PRC2 loss induces chemoresistance by repressing apoptosis in T cell acute lymphoblastic leukemia. J Exp Med. 2018 12 03; 215(12):3094-3114. View in: Pubmed

      • Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 01 03; 133(1):7-17. View in: Pubmed

      • Targeted inhibition of PI3Ka/d is synergistic with BCL-2 blockade in genetically defined subtypes of DLBCL. Blood. 2019 01 03; 133(1):70-80. View in: Pubmed

      • Splicing modulation sensitizes chronic lymphocytic leukemia cells to venetoclax by remodeling mitochondrial apoptotic dependencies. JCI Insight. 2018 10 04; 3(19). View in: Pubmed

      • BCL-2 inhibition in AML: an unexpected bonus? Blood. 2018 09 06; 132(10):1007-1012. View in: Pubmed

      • Phosphorylation switches Bax from promoting to inhibiting apoptosis thereby increasing drug resistance. EMBO Rep. 2018 09; 19(9). View in: Pubmed

      • PPM1D-truncating mutations confer resistance to chemotherapy and sensitivity to PPM1D inhibition in hematopoietic cells. Blood. 2018 09 13; 132(11):1095-1105. View in: Pubmed

      • Metabolomic and BH3 profiling of esophageal cancers: novel assessment methods for precision therapy. BMC Gastroenterol. 2018 Jun 22; 18(1):94. View in: Pubmed

      • Statins enhance efficacy of venetoclax in blood cancers. Sci Transl Med. 2018 06 13; 10(445). View in: Pubmed

      • Targeting B-Cell Lymphoma 2: A Lethal Shortcut in Del(17p) Chronic Lymphocytic Leukemia. J Clin Oncol. 2018 07 01; 36(19):1991-1993. View in: Pubmed

      • Diminished apoptotic priming and ATM signalling confer a survival advantage onto aged haematopoietic stem cells in response to DNA damage. Nat Cell Biol. 2018 04; 20(4):413-421. View in: Pubmed

      • MEF2C Phosphorylation Is Required for Chemotherapy Resistance in Acute Myeloid Leukemia. Cancer Discov. 2018 04; 8(4):478-497. View in: Pubmed

      • 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 01 30; 115(5):E886-E895. View in: Pubmed

      • 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 02; 19(2):216-228. View in: Pubmed

      • ER Stress Signaling Promotes the Survival of Cancer "Persister Cells" Tolerant to EGFR Tyrosine Kinase Inhibitors. Cancer Res. 2018 02 15; 78(4):1044-1057. View in: Pubmed

      • Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis. Sci Transl Med. 2017 Dec 13; 9(420). View in: Pubmed

      • 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. View in: Pubmed

      • Overcoming mutational complexity in acute myeloid leukemia by inhibition of critical pathways. Sci Transl Med. 2017 Oct 25; 9(413). View in: Pubmed

      • BCL-XL directly modulates RAS signalling to favour cancer cell stemness. Nat Commun. 2017 10 24; 8(1):1123. View in: Pubmed

      • Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma. Nat Med. 2017 Nov; 23(11):1342-1351. View in: Pubmed

      • Inhibition of USP10 induces degradation of oncogenic FLT3. Nat Chem Biol. 2017 Dec; 13(12):1207-1215. View in: Pubmed

      • Functional precision cancer medicine-moving beyond pure genomics. Nat Med. 2017 Sep 08; 23(9):1028-1035. View in: Pubmed

      • Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1. Elife. 2017 06 08; 6. View in: Pubmed

      • Synergistic interactions with PI3K inhibition that induce apoptosis. Elife. 2017 05 31; 6. View in: Pubmed

      • Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection. Elife. 2017 04 20; 6. View in: Pubmed

      • Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature. 2017 03 16; 543(7645):428-432. View in: Pubmed

      • 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. View in: Pubmed

      • Bruton's tyrosine kinase inhibition increases BCL-2 dependence and enhances sensitivity to venetoclax in chronic lymphocytic leukemia. Leukemia. 2017 10; 31(10):2075-2084. View in: Pubmed

      • 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. View in: Pubmed

      • Tight Sequestration of BH3 Proteins by BCL-xL at Subcellular Membranes Contributes to Apoptotic Resistance. Cell Rep. 2016 12 20; 17(12):3347-3358. View in: Pubmed

      • Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors. FEBS Lett. 2017 Jan; 591(1):240-251. View in: Pubmed

      • Blastic Plasmacytoid Dendritic Cell Neoplasm Is Dependent on BCL2 and Sensitive to Venetoclax. Cancer Discov. 2017 02; 7(2):156-164. View in: Pubmed

      • S63845, an MCL-1 Selective BH3 Mimetic: Another Arrow in Our Quiver. Cancer Cell. 2016 Dec 12; 30(6):834-835. View in: Pubmed

      • Genomic evolution and chemoresistance in germ-cell tumours. Nature. 2016 11 30; 540(7631):114-118. View in: Pubmed

      • To Prime, or Not to Prime: That Is the Question. Cold Spring Harb Symp Quant Biol. 2016; 81:131-140. View in: Pubmed

      • Cristae remodeling causes acidification detected by integrated graphene sensor during mitochondrial outer membrane permeabilization. Sci Rep. 2016 10 27; 6:35907. View in: Pubmed

      • 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. View in: Pubmed

      • 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. View in: Pubmed

      • Functionally identifiable apoptosis-insensitive subpopulations determine chemoresistance in acute myeloid leukemia. J Clin Invest. 2016 10 03; 126(10):3827-3836. View in: Pubmed

      • 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. View in: Pubmed

      • The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 07 11; 30(1):183. View in: Pubmed

      • iBH3: simple, fixable BH3 profiling to determine apoptotic priming in primary tissue by flow cytometry. Biol Chem. 2016 07 01; 397(7):671-8. View in: Pubmed

      • Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition. Nat Commun. 2016 05 20; 7:11589. View in: Pubmed

      • BOK: Oddball of the BCL-2 Family. Trends Cell Biol. 2016 06; 26(6):389-390. View in: Pubmed

      • 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. View in: Pubmed

      • The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 04 11; 29(4):574-586. View in: Pubmed

      • Dynamic BH3 profiling-poking cancer cells with a stick. Mol Cell Oncol. 2016 May; 3(3):e1040144. View in: Pubmed

      • Defining specificity and on-target activity of BH3-mimetics using engineered B-ALL cell lines. Oncotarget. 2016 Mar 08; 7(10):11500-11. View in: Pubmed

      • Mitochondria-Judges and Executioners of Cell Death Sentences. Mol Cell. 2016 Mar 03; 61(5):695-704. View in: Pubmed

      • 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. View in: Pubmed

      • 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. View in: Pubmed

      • Cell Death and Cancer Therapy: Don't Forget to Kill the Cancer Cell! Clin Cancer Res. 2015 Nov 15; 21(22):5015-20. View in: Pubmed

      • Precision medicine for cancer with next-generation functional diagnostics. Nat Rev Cancer. 2015 Dec; 15(12):747-56. View in: Pubmed

      • 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. View in: Pubmed

      • Direct and immune-mediated cytotoxicity of interleukin-21 contributes to antitumor effects in mantle cell lymphoma. Blood. 2015 Sep 24; 126(13):1555-64. View in: Pubmed

      • 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. View in: Pubmed

      • Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia. Cancer Cell. 2015 Jul 13; 28(1):29-41. View in: Pubmed

      • Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy. Cell. 2015 Feb 26; 160(5):977-989. View in: Pubmed

      • RAS signaling promotes resistance to JAK inhibitors by suppressing BAD-mediated apoptosis. Sci Signal. 2014 Dec 23; 7(357):ra122. View in: Pubmed

      • Potent and specific peptide inhibitors of human pro-survival protein Bcl-xL. J Mol Biol. 2015 Mar 27; 427(6 Pt B):1241-1253. View in: Pubmed

      • Bcl-xL controls a switch between cell death modes during mitotic arrest. Cell Death Dis. 2014; 5:e1429. View in: Pubmed

      • Designed BH3 peptides with high affinity and specificity for targeting Mcl-1 in cells. ACS Chem Biol. 2014 Sep 19; 9(9):1962-8. View in: Pubmed

      • 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. View in: Pubmed

      • 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. View in: Pubmed

      • Bcl-xL controls a switch between cell death modes during mitotic arrest. Cell Death Dis. 2014 Jun 12; 5:e1291. View in: Pubmed

      • APC(Cdc20) suppresses apoptosis through targeting Bim for ubiquitination and destruction. Dev Cell. 2014 May 27; 29(4):377-91. View in: Pubmed

      • Increased mitochondrial apoptotic priming of human regulatory T cells after allogeneic hematopoietic stem cell transplantation. Haematologica. 2014 Sep; 99(9):1499-508. View in: Pubmed

      • Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis. Apoptosis. 2014 Apr; 19(4):629-42. View in: Pubmed

      • Decreased mitochondrial priming determines chemoresistance of colon cancer stem cells. Cell Death Differ. 2014 Jul; 21(7):1170-7. View in: Pubmed

      • 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. View in: Pubmed

      • Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia. Cancer Discov. 2014 Mar; 4(3):362-75. View in: Pubmed

      • BID preferentially activates BAK while BIM preferentially activates BAX, affecting chemotherapy response. Mol Cell. 2013 Sep 26; 51(6):751-65. View in: Pubmed

      • Mitochondria: gatekeepers of response to chemotherapy. Trends Cell Biol. 2013 Dec; 23(12):612-9. View in: Pubmed

      • High mitochondrial priming sensitizes hESCs to DNA-damage-induced apoptosis. Cell Stem Cell. 2013 Oct 03; 13(4):483-91. View in: Pubmed

      • Overcoming stroma-mediated treatment resistance in chronic lymphocytic leukemia through BCL-2 inhibition. Leuk Lymphoma. 2013 Aug; 54(8):1823-5. View in: Pubmed

      • p53 regulates a non-apoptotic death induced by ROS. Cell Death Differ. 2013 Nov; 20(11):1465-74. View in: Pubmed

      • BH3 profiling in whole cells by fluorimeter or FACS. Methods. 2013 Jun 01; 61(2):156-64. View in: Pubmed

      • BCL-2 inhibition: stemming the tide of myeloid malignancies. Cell Stem Cell. 2013 Mar 07; 12(3):269-70. View in: Pubmed

      • ABT-199: taking dead aim at BCL-2. Cancer Cell. 2013 Feb 11; 23(2):139-41. View in: Pubmed

      • 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. View in: Pubmed

      • Priming BCL-2 to kill: the combination therapy of tamoxifen and ABT-199 in ER+ breast cancer. Breast Cancer Res. 2013; 15(5):317. View in: Pubmed

      • Relative mitochondrial priming of myeloblasts and normal HSCs determines chemotherapeutic success in AML. Cell. 2012 Oct 12; 151(2):344-55. View in: Pubmed

      • Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors. Cancer Discov. 2012 Oct; 2(10):934-47. View in: Pubmed

      • Decreased mitochondrial apoptotic priming underlies stroma-mediated treatment resistance in chronic lymphocytic leukemia. Blood. 2012 Oct 25; 120(17):3501-9. View in: Pubmed

      • BCL2 suppresses PARP1 function and nonapoptotic cell death. Cancer Res. 2012 Aug 15; 72(16):4193-203. View in: Pubmed

      • Targeting the B-cell lymphoma/leukemia 2 family in cancer. J Clin Oncol. 2012 Sep 01; 30(25):3127-35. View in: Pubmed

      • 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. View in: Pubmed

      • BH3 profiling--measuring integrated function of the mitochondrial apoptotic pathway to predict cell fate decisions. Cancer Lett. 2013 May 28; 332(2):202-5. View in: Pubmed

      • Who put the "A" in Atg12: autophagy or apoptosis? Mol Cell. 2011 Dec 23; 44(6):844-5. View in: Pubmed

      • P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment. Blood. 2012 Feb 09; 119(6):1468-78. View in: Pubmed

      • Pretreatment mitochondrial priming correlates with clinical response to cytotoxic chemotherapy. Science. 2011 Nov 25; 334(6059):1129-33. View in: Pubmed

      • Targeting Bcl-2 in CLL: cui bono? Blood. 2011 Sep 29; 118(13):3453-4. View in: Pubmed

      • The Bcl-2 repertoire of mesothelioma spheroids underlies acquired apoptotic multicellular resistance. Cell Death Dis. 2011 Jun 23; 2:e174. View in: Pubmed

      • A new face of BCL-2 inhibition in CLL. Blood. 2011 Mar 10; 117(10):2750-1. View in: Pubmed

      • 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. View in: Pubmed

      • 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. View in: Pubmed

      • Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1. Blood. 2010 Apr 22; 115(16):3304-13. View in: Pubmed

      • The landscape of somatic copy-number alteration across human cancers. Nature. 2010 Feb 18; 463(7283):899-905. View in: Pubmed

      • BH3-only proteins and their effects on cancer. Adv Exp Med Biol. 2010; 687:49-63. View in: Pubmed

      • 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. View in: Pubmed

      • Parkin selectively alters the intrinsic threshold for mitochondrial cytochrome c release. Hum Mol Genet. 2009 Nov 15; 18(22):4317-28. View in: Pubmed

      • Aurora kinase A is a target of Wnt/beta-catenin involved in multiple myeloma disease progression. Blood. 2009 Sep 24; 114(13):2699-708. View in: Pubmed

      • Hiding from ABT-737 in lymph nodes. Blood. 2009 Apr 30; 113(18):4132-3. View in: Pubmed

      • Puma strikes Bax. J Cell Biol. 2009 Apr 20; 185(2):189-91. View in: Pubmed

      • Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci. 2009 Feb 15; 122(Pt 4):437-41. View in: Pubmed

      • Mimicking the BH3 domain to kill cancer cells. Oncogene. 2008 Dec; 27 Suppl 1:S149-57. View in: Pubmed

      • 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. View in: Pubmed

      • 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. View in: Pubmed

      • Regulation of Bcl-2 family proteins by posttranslational modifications. Curr Mol Med. 2008 Mar; 8(2):102-18. View in: Pubmed

      • Diagnosing and exploiting cancer's addiction to blocks in apoptosis. Nat Rev Cancer. 2008 Feb; 8(2):121-32. View in: Pubmed

      • 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. View in: Pubmed

      • 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. View in: Pubmed

      • Apoptosis Dysregulation in CLL. Chronic Lymphocytic Leukemia. 2008. View in: Pubmed

      • 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. View in: Pubmed

      • BH3 domains define selective inhibitory interactions with BHRF-1 and KSHV BCL-2. Cell Death Differ. 2008 Mar; 15(3):580-8. View in: Pubmed

      • BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia. Blood. 2008 Feb 15; 111(4):2300-9. View in: Pubmed

      • 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. View in: Pubmed

      • 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. View in: Pubmed

      • Restoring cancer's death sentence. Cancer Cell. 2006 Nov; 10(5):343-5. View in: Pubmed

      • Laying the foundations of programmed cell death. Cell Death Differ. 2006 Aug; 13(8):1245-7. View in: Pubmed

      • Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell. 2006 May; 9(5):351-65. View in: Pubmed

      • BH3 peptidomimetics potently activate apoptosis and demonstrate single agent efficacy in neuroblastoma. Oncogene. 2006 Aug 03; 25(33):4525-33. View in: Pubmed

      • Growth factor withdrawal and apoptosis: the middle game. Mol Cell. 2006 Mar 17; 21(6):728-30. View in: Pubmed

      • 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. View in: Pubmed

      • Pharmacological manipulation of Bcl-2 family members to control cell death. J Clin Invest. 2005 Oct; 115(10):2648-55. View in: Pubmed

      • BCL-2: found bound and drugged! Trends Mol Med. 2005 Oct; 11(10):442-4. View in: Pubmed

      • An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005 Jun 02; 435(7042):677-81. View in: Pubmed

      • Lymphoid Neoplasms. Molecular Hematology. 2005; 105-114. View in: Pubmed

      • Antiapoptotic BCL-2 is required for maintenance of a model leukemia. Cancer Cell. 2004 Sep; 6(3):241-9. View in: Pubmed

      • Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature. 2003 Dec 11; 426(6967):671-6. View in: Pubmed

      • Smallpox and smallpox vaccination. N Engl J Med. 2003 May 08; 348(19):1920-5; author reply 1920-5. View in: Pubmed

      • BH3 domains as BCL-2 inhibitors: prototype cancer therapeutics. Expert Opin Biol Ther. 2003 Apr; 3(2):293-304. View in: Pubmed

      • Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell. 2002 Sep; 2(3):183-92. View in: Pubmed

      • Cancer, coagulation, and anticoagulation. Oncologist. 1999; 4(6):443-9. View in: Pubmed

      • The importance of intramolecular ion pairing in intermediate filaments. Proc Natl Acad Sci U S A. 1995 Jan 03; 92(1):92-6. View in: Pubmed

      • Genetic bases of epidermolysis bullosa simplex and epidermolytic hyperkeratosis. J Invest Dermatol. 1994 Nov; 103(5 Suppl):25S-30S. View in: Pubmed

      • 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. View in: Pubmed

      • Keratin Mutations and Heritable Skin Disease. 1993. View in: Pubmed

      • The genetic basis of epidermolytic hyperkeratosis: a disorder of differentiation-specific epidermal keratin genes. Cell. 1992 Sep 04; 70(5):811-9. View in: Pubmed

      • 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. View in: Pubmed

      • Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: genetic and functional analyses. Cell. 1991 Sep 20; 66(6):1301-11. View in: Pubmed

      • Pancreas-graft immunogenicity and pretreatment with anti-class II monoclonal antibodies. Diabetes. 1989 Jan; 38 Suppl 1:104-8. View in: Pubmed

      • 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. View in: Pubmed

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      Dana-Farber Cancer Institute

      450 Brookline Avenue Mayer 429 Boston, MA 02215
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      42.3374, -71.1082