Evidence mapPaperPMID 39126100Full record

ArticleInternational journal of molecular sciences2024

Discovery of NFκB2-Coordinated Dual Regulation of Mitochondrial and Nuclear Genomes Leads to an Effective Therapy for Acute Myeloid Leukemia.

Yi Xu, David J Baylink, Jeffrey Xiao, Lily Tran, Vinh Nguyen, Brandon Park, Ismael Valladares, Scott Lee, Kevin Codorniz, Laren Tan and 6 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
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

1 citing paper in PubMed.

  1. Article
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.

Yi XuDivision of Hematology and Oncology, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
David J BaylinkDivision Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Jeffrey XiaoDivision Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Lily TranDivision Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Vinh NguyenDivision Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Brandon ParkDivision Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Ismael ValladaresDivision Regenerative Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Scott LeeDivision of Endocrinology, Diabetes & Metabolism, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Kevin CodornizDivision of Endocrinology, Diabetes & Metabolism, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Laren TanDivision of Pulmonary, Critical Care, Hyperbaric and Sleep Medicine, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Chien-Shing ChenDivision of Hematology and Oncology, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.ORCID 0000-0002-0157-4140
Hisham Abdel-AzimDivision of Hematology and Oncology, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Mark E ReevesDivision of Hematology and Oncology, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Hamid MirshahidiDivision of Hematology and Oncology, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Guido MarcucciDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA 91010, USA.
Huynh CaoDivision of Hematology and Oncology, Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.

Funding

Loma Linda University GRASP2020
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) has a poor survival rate for both pediatric and adult patients due to its frequent relapse. To elucidate the bioenergetic principle underlying AML relapse, we investigated the transcriptional regulation of mitochondrial-nuclear dual genomes responsible for metabolic plasticity in treatment-resistant blasts. Both the gain and loss of function results demonstrated that NFκB2, a noncanonical transcription factor (TF) of the NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) family, can control the expression of TFAM (mitochondrial transcription factor A), which is known to be essential for metabolic biogenesis. Furthermore, genetic tracking and promoter assays revealed that NFκB2 is in the mitochondria and can bind the specific "TTGGGGGGTG" region of the regulatory D-loop domain to activate the light-strand promoter (LSP) and heavy-strand promoter 1 (HSP1), promoters of the mitochondrial genome. Based on our discovery of NFκB2's novel function of regulating mitochondrial-nuclear dual genomes, we explored a novel triplet therapy including inhibitors of NFκB2, tyrosine kinase, and mitochondrial ATP synthase that effectively eliminated primary AML blasts with mutations of the FMS-related receptor tyrosine kinase 3 (

Indexed as

Genome, MitochondrialLeukemia, Myeloid, AcuteCell Line, TumorCell NucleusDNA-Binding ProteinsGene Expression Regulation, LeukemicHumansMitochondriaMitochondrial ProteinsPromoter Regions, GeneticTranscription FactorsDNA-Binding ProteinsMitochondrial Proteinsmitochondrial transcription factor ATranscription FactorsAMLATPFLT3gilteritinibmetabolismmitochondrionNFκB2NRF1TFAM

Identifiers

PMID39126100
PMCPMC11313218

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.