Evidence map›Paper›PMID 30623427›Full record

ArticleJournal of cellular physiology2019

The Bcl-2 inhibitor venetoclax inhibits Nrf2 antioxidant pathway activation induced by hypomethylating agents in AML.

Le Xuan Truong Nguyen, Estelle Troadec, Arjun Kalvala, Bijender Kumar, Dinh Hoa Hoang, Domenico Viola, Bin Zhang, Dang Quan Nguyen, Ibrahim Aldoss, Lucy Ghoda and 6 more

Abstract read
In one paragraph

Article in Journal of cellular physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

58 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  3. Nucleolin Alterations and ROS Production Associate With Sensitivity of AML Cells to Venetoclax.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 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

16 authors.

Le Xuan Truong NguyenGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California.ORCID 0000-0001-5464-0861
Estelle TroadecGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California.
Arjun KalvalaGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California.
Bijender KumarGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California.
Dinh Hoa HoangGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California.
Domenico ViolaGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California.
Bin ZhangGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California.
Dang Quan NguyenDepartment of Medical Biotechnology, Biotechnology Center of Ho Chi Minh City, Ho Chi Minh City, Vietnam.
Ibrahim AldossDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, California.
Lucy GhodaGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California.
Elizabeth BuddeDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, California.
Flavia PichiorriGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California.
Steven RosenDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, California.
Stephen J FormanDepartment of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, California.
Guido MarcucciGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California.
Vinod PullarkatGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California.

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
NCI NIH HHS P30 CA033572NCI NIH HHS P30CA033572
6 · The paper itself

Abstract

Induction of reactive oxygen species (ROS), an important process for the cytotoxicity of various acute myeloid leukemia (AML) therapies including hypomethylating agents (HMAs), concurrently activates the NF-E2-related factor 2 (Nrf2) antioxidant response pathway which in turn results in induction of antioxidant enzymes that neutralize ROS. In this study, we demonstrated that Nrf2 inhibition is an additional mechanism responsible for the marked antileukemic activity in AML seen with the combination of HMAs and venetoclax (ABT-199). HMA and venetoclax combined treatment augmented mitochondrial ROS induction and apoptosis compared with treatment HMA alone. Treatment of AML cell lines as well as primary AML cells with venetoclax disrupted HMA decitabine-increased nuclear translocation of Nrf2 and induction of downstream antioxidant enzymes including heme oxygenase-1 and NADP-quinone oxidoreductase-1. Venetoclax treatment also leads to dissociation of B-cell lymphoma 2 from the Nrf2/Keap-1 complex and targets Nrf2 to ubiquitination and proteasomal degradation. Thus, our results here demonstrated an undiscovered mechanism underlying synergistic effect of decitabine and venetoclax in AML cells, elucidating for impressive results in antileukemic activity against AML in preclinical and early clinical studies by combined treatment of these drugs.

Indexed as

Active Transport, Cell NucleusAntioxidant Response ElementsApoptosisBone MarrowBridged Bicyclo Compounds, HeterocyclicCell Line, TumorDecitabineDNA MethylationDrug SynergismFemaleGene Expression Regulation, LeukemicHeme Oxygenase-1HumansKelch-Like ECH-Associated Protein 1Leukemia, Myeloid, AcuteMaleBCL2 protein, humanBridged Bicyclo Compounds, HeterocyclicDecitabineHeme Oxygenase-1Kelch-Like ECH-Associated Protein 1NAD(P)H Dehydrogenase (Quinone)NFE2L2 protein, humanNF-E2-Related Factor 2NQO1 protein, humanProto-Oncogene Proteins c-bcl-2Reactive Oxygen SpeciesSulfonamidesvenetoclaxacute myeloid leukemiaantioxidant responsehypomethylating agentsNrf2reactive oxygen speciesubiquitinationvenetoclax

Identifiers

PMID30623427
PMCPMC8852851

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Registered trials

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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.