Evidence map›Paper›PMID 37088914›Full record

ArticleCancer discovery2023

Mitophagy Promotes Resistance to BH3 Mimetics in Acute Myeloid Leukemia.

Christina Glytsou, Xufeng Chen, Emmanouil Zacharioudakis, Wafa Al-Santli, Hua Zhou, Bettina Nadorp, Soobeom Lee, Audrey Lasry, Zhengxi Sun, Dimitrios Papaioannou and 11 more

Open access · greenAbstract read
In one paragraph

Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
15.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
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  10. Prognostic model construction and drug prediction in colorectal cancer using mitochondrial programmed cell death-related genes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  18. Frontiers in oncology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 6 institutions in 2 countries.

Christina Glytsou *Department of Pathology, NYU Grossman School of Medicine, New York, New York.ORCID 0000-0002-6260-338X
Xufeng Chen *Department of Pathology, NYU Grossman School of Medicine, New York, New York.ORCID 0000-0001-8325-971X
Emmanouil Zacharioudakis *Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York.ORCID 0000-0003-2781-9553
Wafa Al-SantliDepartment of Pathology, NYU Grossman School of Medicine, New York, New York.ORCID 0009-0001-6332-8789
Hua ZhouApplied Bioinformatics Laboratories, NYU School of Medicine, New York, New York.ORCID 0000-0003-1822-1306
Bettina NadorpDepartment of Pathology, NYU Grossman School of Medicine, New York, New York.ORCID 0000-0003-1974-8425
Soobeom LeeDepartment of Biology, New York University, New York, New York.ORCID 0000-0002-1541-3751
Audrey LasryDepartment of Pathology, NYU Grossman School of Medicine, New York, New York.ORCID 0000-0001-6588-6760
Zhengxi SunDepartment of Pathology, NYU Grossman School of Medicine, New York, New York.ORCID 0000-0002-9252-2871
Dimitrios PapaioannouDepartment of Pathology, NYU Grossman School of Medicine, New York, New York.ORCID 0000-0003-1404-279X
Michael CammerMicroscopy Core, Division of Advanced Research Technologies, New York University Grossman School of Medicine, New York, New York.ORCID 0000-0003-4930-1739
Kun WangDepartment of Pathology, NYU Grossman School of Medicine, New York, New York.ORCID 0009-0006-8708-6354
Tomasz ZalSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-3469-4261
Malgorzata Anna ZalSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-1015-3954
Bing Z CarterSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-0076-0889
Jo IshizawaSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-8566-7370
Raoul TibesAstraZeneca, Cambridge, United Kingdom.ORCID 0000-0002-1372-8733
Aristotelis TsirigosDepartment of Pathology, NYU Grossman School of Medicine, New York, New York.ORCID 0000-0002-7512-8477
Michael AndreeffSection of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-1144-1958
Evripidis GavathiotisDepartment of Biochemistry, Albert Einstein College of Medicine, Bronx, New York.ORCID 0000-0001-6319-8331
Iannis AifantisDepartment of Pathology, NYU Grossman School of Medicine, New York, New York.ORCID 0000-0001-6857-1035
NYU Langone Health · USThe University of Texas MD Anderson Cancer Center · USNew York University · USAlbert Einstein College of Medicine · USAstraZeneca (United Kingdom) · GBRutgers, The State University of New Jersey · US

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI STEVEN C. ALMO · 1985 to 2026
$111.2M
Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ANIRBAN MAITRA · 1985 to 2026
$83.1M
Role of Autophagy in T Cell Function and Immunosenescence (Project 3)P01AG031782 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI BRAVO-CORDERO, JOSE JAVIER · 2009 to 2024
$36.2M
The impact of changes in chromatin architecture on cancer phenotypes and tumor progressionP01CA229086 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Jane Amanda Skok · 2019 to 2026
$17.0M
Role of TET2 mutations in malignant transformation and acute myeloid leukemiaR01CA173636 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI AIFANTIS, IANNIS, LEVINE, ROSS L · 2013 to 2022
$6.3M
Small Molecule Activators of Pro-apoptotic BAX for Cancer TherapyR01CA178394 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI GAVATHIOTIS, EVRIPIDIS · 2014 to 2024
$3.7M
Targeting an RNA Binding Protein Network in Acute Myeloid LeukemiaR01CA242020 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR, AIFANTIS, IANNIS · 2020 to 2024
$2.7M
mRNA stability and its impact on hematopoiesis and acute leukemiaR01CA266212 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Iannis Aifantis · 2022 to 2026
$2.7M
The cohesin complex as a tumor suppressor in myeloid leukemiaR01CA216421 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS, LEVINE, ROSS L · 2017 to 2021
$2.5M
Mechanisms of enhancer regulation in leukemiaR01CA228135 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS · 2019 to 2023
$2.5M
Mapping cancer micro-environments for acute leukemiaR01CA202025 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS, SCHWAB, SUSAN RUTH · 2016 to 2020
$2.3M
Post-translational control of cancer cell stress response and metastasisR01CA202027 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS, HERNANDO, EVA · 2016 to 2020
$2.3M
NCI NIH HHS K99 CA252602NCI NIH HHS P01 CA229086NCI NIH HHS P30 CA013330NCI NIH HHS P30 CA016087NCI NIH HHS R00 CA252602NCI NIH HHS R01 CA173636NCI NIH HHS R01 CA178394NCI NIH HHS R01 CA202025NCI NIH HHS R01 CA202027NCI NIH HHS R01 CA216421NCI NIH HHS R01 CA228135NCI NIH HHS R01 CA238229NCI NIH HHS R01 CA242020NCI NIH HHS R01 CA266212NCI NIH HHS R01 CA283574NCRR NIH HHS S10 RR023704NCRR NIH HHS S10 RR024708NCRR NIH HHS S10 RR029552NIA NIH HHS P01 AG031782
6 · The paper itself

Abstract

BH3 mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is used clinically in combination with hypomethylating agents for the treatment of AML. Moreover, MCL1 or dual BCL-2/BCL-xL antagonists are under investigation. Yet, resistance to single or combinatorial BH3-mimetic therapies eventually ensues. Integration of multiple genome-wide CRISPR/Cas9 screens revealed that loss of mitophagy modulators sensitizes AML cells to various BH3 mimetics targeting different BCL-2 family members. One such regulator is MFN2, whose protein levels positively correlate with drug resistance in patients with AML. MFN2 overexpression is sufficient to drive resistance to BH3 mimetics in AML. Insensitivity to BH3 mimetics is accompanied by enhanced mitochondria-endoplasmic reticulum interactions and augmented mitophagy flux, which acts as a prosurvival mechanism to eliminate mitochondrial damage. Genetic or pharmacologic MFN2 targeting synergizes with BH3 mimetics by impairing mitochondrial clearance and enhancing apoptosis in AML. SIGNIFICANCE: AML remains one of the most difficult-to-treat blood cancers. BH3 mimetics represent a promising therapeutic approach to eliminate AML blasts by activating the apoptotic pathway. Enhanced mitochondrial clearance drives resistance to BH3 mimetics and predicts poor prognosis. Reverting excessive mitophagy can halt BH3-mimetic resistance in AML. This article is highlighted in the In This Issue feature, p. 1501.

Indexed as

Antineoplastic AgentsLeukemia, Myeloid, AcuteApoptosisCell DeathCell Line, TumorHumansMitophagyMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-bcl-2Antineoplastic AgentsMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-bcl-2

Identifiers

PMID37088914
PMCPMC10330144
OpenAlexW4366821995

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.