ArticleCancer cell2019
Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies.
Registry-linked trialOpen access · hybridAbstract read
In one paragraph
Article in Cancer cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04666649 (Pegcrisantaspase in Combination With Venetoclax for Treatment of Relapsed or Refractory Acute Myeloid Leukemia), which is not on this map. Cited by 238 papers.
0numbers the graph read from it
0cells of the map it votes in
238citing papers in PubMed
24.4field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Pegcrisantaspase in Combination With Venetoclax for Treatment of Relapsed or Refractory Acute Myeloid Leukemia
Who cites it
238 citing papers in PubMed, 352 citations in OpenAlex.
- A high-density CRISPR activation platform for mapping cancer dependencies and resistance pathways ex vivo and in vivo.Science advances · 2026Article
- Protein-protein interactions as therapeutic targets in breast cancer: integrated computational and experimental advances, mechanisms and clinical translation.Molecular biology reports · 2026Review
- ZMYM3 mutations modulate histone acetylation and cooperate with NOTCH1 mutations in chronic lymphocytic leukemia.Blood advances · 2026Article
- Inhibition of PRMT5 sensitizes B-cell non-Hodgkin lymphoma cells to both intrinsic and extrinsic apoptotic cell death.Blood neoplasia · 2026Article
- The Natural Quassinoid Brusatol Enhances Venetoclax Efficacy and Overcomes Resistance in Myeloid Leukemias.Cancer science · 2026Article
- Translocation t(11;14) and BCL2-inhibition in multiple myeloma.Haematologica · 2026Review
- Cancer-Associated BCL-2 Mutants Reveal Mechanisms Towards Venetoclax Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Anti-apoptotic BCL-2 family proteins: from regulatory networks to therapeutic targeting.Oncogenesis · 2026Review
- Inhibition of ADSS2-mediated de novo AMP biosynthesis re-sensitizes acute myeloid leukemia to BH3 mimetics.Nature cancer · 2026Article
- CCL19bioRxiv : the preprint server for biology · 2026Article
- Venetoclax retreatment in chronic lymphocytic leukemia is biologically rational and clinically effective.Blood advances · 2026Review
- Acid ceramidase inhibition enhances BCL-2 targeting in venetoclax-resistant acute myeloid leukemia.Blood neoplasia · 2026Article
- Hematopoietic Aging and Leukemia: Mechanistic and Therapeutic Insights.International journal of molecular sciences · 2026Review
- mRNA lipid-nanoparticle-mediated mitochondrial apoptosis augments adoptive T cell immunotherapy.Cell reports. Medicine · 2026Article
- U2AF regulates the translation and localization of nuclear-encoded mitochondrial mRNAs.Molecular cell · 2026Article
- A STAT3 degrader demonstrates efficacy in venetoclax resistant acute myeloid leukemia.Leukemia · 2026Article
- Effects and molecular mechanism of inhibiting p53 signaling pathway by NSUN4 on the resistance to BCL-2 inhibitor for diffuse large B-cell lymphoma.Clinical and experimental medicine · 2026Article
- Resistance to Targeted Therapy in AML: Current Challenges and Emerging Treatment Strategies.Journal of clinical medicine · 2026Review
- When Targeted Therapy Falls Short: Unraveling Resistance Mechanisms in Chronic Lymphocytic Leukemia.Current hematologic malignancy reports · 2026Review
- Article
178 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
41 authors at 9 institutions in 3 countries.
Romain GuièzeDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA; CHU de Clermont-Ferrand, 63000 Clermont-Ferrand, France; Université Clermont Auvergne, EA7453 CHELTER, 63000 Clermont-Ferrand, France.
Vivian M LiuDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Harvard Medical School, Boston, MA 02215, USA.
Daniel RosebrockBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Alexis A JourdainBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA; Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
María Hernández-SánchezDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer-IBMCC, Universidad de Salamanca, 37007 Salamanca, Spain; Servicio de Hematología, Hospital Universitario de Salamanca, 37007 Salamanca, Spain.
Aina Martinez ZuritaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jing SunDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Elisa Ten HackenDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA.
Kaitlyn BaranowskiDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA.
Philip A ThompsonDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Jin-Mi HeoDepartment of Cell Biology, Harvard Medical School, Boston, MA 02215, USA.
Zachary CartunDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA.
Ozan AygünBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
J Bryan IorgulescuDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Harvard Medical School, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA.
Wandi ZhangDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA.
Giulia NotarangeloDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Harvard Medical School, Boston, MA 02215, USA.
Dimitri LivitzBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Shuqiang LiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Matthew S DavidsDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
Anat BiranDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA.
Stacey M FernandesDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA.
Jennifer R BrownDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
Ana LakoCenter for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Zoe B CiantraCenter for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Matthew A LawlorHarvard Medical School, Boston, MA 02215, USA; Massachusetts General Hospital Cancer Center, Boston, MA 02214, USA.
Derin B KeskinDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA.
Namrata D UdeshiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
William G WierdaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Kenneth J LivakDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA.
Anthony G LetaiDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
Donna NeubergHarvard Medical School, Boston, MA 02215, USA; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
J Wade HarperDepartment of Cell Biology, Harvard Medical School, Boston, MA 02215, USA.
Steven A CarrBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Federica PiccioniBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Christopher J OttHarvard Medical School, Boston, MA 02215, USA; Massachusetts General Hospital Cancer Center, Boston, MA 02214, USA.
Ignaty LeshchinerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cory M JohannessenBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
John DoenchBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Vamsi K MoothaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA; Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Gad GetzBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA; Massachusetts General Hospital Cancer Center, Boston, MA 02214, USA.
Catherine J WuDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA. Electronic address: cwu@partners.org.
Broad Institute · USDana-Farber Cancer Institute · USHarvard University · USMassachusetts General Hospital · USThe University of Texas MD Anderson Cancer Center · USBrigham and Women's Hospital · USCentre Hospitalier Universitaire de Clermont-Ferrand · FRComplejo Hospitalario de Salamanca · ESHoward Hughes Medical Institute · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MTissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5MProteomicsP01CA206978 · NCI · DANA-FARBER CANCER INST · PI WU, CATHERINE JU-YING · 2016 to 2025
$17.0MVASCULAR, PULMONARY AND RENAL INJURYT32HL007627 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GIMBRONE, MICHAEL A, MITCHELL, RICHARD N · 1985 to 2019
$12.7MPersonal tumor neoantigens for immunity against chronic lymphocytic leukemiaR01CA155010 · NCI · DANA-FARBER CANCER INST · PI Catherine Ju-Ying Wu · 2011 to 2026
$9.6MMICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALSU01CA214125 · NCI · BAYLOR COLLEGE OF MEDICINE · PI ANURAG, MEENAKSHI, CARR, STEVEN A · 2017 to 2021
$7.0MCenter of Excellence for High Throughput Proteogenomic CharacterizationU24CA210986 · NCI · BROAD INSTITUTE, INC. · PI CARR, STEVEN A, GILLETTE, MICHAEL A · 2016 to 2020
$6.4MITSC for Leukemia: Novel Molecular strategies for NCTN "Individualized" TherapiesUG1CA233338 · NCI · UNIVERSITY OF CINCINNATI · PI BYRD, JOHN C. · 2019 to 2025
$4.5MMitochondrial Parts, Pathways, and PathogenesisR35GM122455 · NIGMS · BROAD INSTITUTE, INC. · PI MOOTHA, VAMSI KRISHNA · 2017 to 2021
$4.0M(PQ8) Genetically faithful murine models for studying disease progression in chronic lymphocytic leukemiaR01CA216273 · NCI · DANA-FARBER CANCER INST · PI WANG, LILI, WU, CATHERINE JU-YING · 2017 to 2021
$3.5MITSC for Leukemia: Novel Molecular Strategies for NCTN: "Individualized" TherapieU10CA180861 · NCI · OHIO STATE UNIVERSITY · PI BLOOMFIELD, CLARA D, MARCUCCI, GUIDO · 2014 to 2018
$3.4MNetwork organization of the human autophagy systemR01GM095567 · NIGMS · HARVARD MEDICAL SCHOOL · PI HARPER, JEFFREY W, KIMMELMAN, ALEC · 2011 to 2018
$3.0MNCI NIH HHS P01 CA081534NCI NIH HHS P01 CA206978NCI NIH HHS P30 CA016672NCI NIH HHS R00 CA190861NCI NIH HHS R01 CA155010NCI NIH HHS R01 CA213442NCI NIH HHS R01 CA216273NCI NIH HHS R21 CA216772NCI NIH HHS U01 CA214125NCI NIH HHS U10 CA180861NCI NIH HHS U24 CA210986NCI NIH HHS UG1 CA233338NHLBI NIH HHS T32 HL007627NIGMS NIH HHS R01 GM095567NIGMS NIH HHS R35 GM122455NINDS NIH HHS R37 NS083524
Abstract
Mitochondrial apoptosis can be effectively targeted in lymphoid malignancies with the FDA-approved B cell lymphoma 2 (BCL-2) inhibitor venetoclax, but resistance to this agent is emerging. We show that venetoclax resistance in chronic lymphocytic leukemia is associated with complex clonal shifts. To identify determinants of resistance, we conducted parallel genome-scale screens of the BCL-2-driven OCI-Ly1 lymphoma cell line after venetoclax exposure along with integrated expression profiling and functional characterization of drug-resistant and engineered cell lines. We identified regulators of lymphoid transcription and cellular energy metabolism as drivers of venetoclax resistance in addition to the known involvement by BCL-2 family members, which were confirmed in patient samples. Our data support the implementation of combinatorial therapy with metabolic modulators to address venetoclax resistance.
Indexed as
AdultAgedAged, 80 and overAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBridged Bicyclo Compounds, HeterocyclicCell Line, TumorClonal EvolutionDisease ProgressionDrug Resistance, NeoplasmEnergy MetabolismFemaleGene Expression Regulation, NeoplasticHumansLeukemia, Lymphocytic, Chronic, B-CellBCL2 protein, humanBridged Bicyclo Compounds, HeterocyclicMCL1 protein, humanMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-bcl-2SulfonamidesvenetoclaxAMPKBCL-2chronic lymphocytic leukemiaclonal evolutionCRISPR/Cas9drug resistancegenome-wide screenmetabolismmitochondrionvenetoclax
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
NCT04666649ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.