Evidence map›Paper›PMID 39283580›Full record

ArticleInternational journal of hematology2024

Mitochondrial dynamics as a potential therapeutic target in acute myeloid leukemia.

Mariko Kinoshita, Yusuke Saito, Kento Otani, Yuya Uehara, Shun Nagasawa, Midori Nakagawa, Ai Yamada, Sachiyo Kamimura, Hiroshi Moritake

Abstract read
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In one paragraph

Article in International journal of hematology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
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

9 authors.

Mariko KinoshitaDivision of Pediatrics, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan. mariko_kinoshita@med.miyazaki-u.ac.jp.ORCID http://orcid.org/0009-0006-3196-5085
Yusuke SaitoDepartment of Medical Oncology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Kento OtaniDivision of Pediatrics, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
Yuya UeharaDivision of Pediatrics, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
Shun NagasawaDivision of Pediatrics, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
Midori NakagawaDivision of Pediatrics, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
Ai YamadaDivision of Pediatrics, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
Sachiyo KamimuraDivision of Pediatrics, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
Hiroshi MoritakeDivision of Pediatrics, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan.

Funding

Japan Society for the Promotion of Science 19K1736
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) cells are highly dependent on oxidative phosphorylation and the mitochondrial dynamics regulated by fusion-related genes MFN1, MFN2, and OPA1 and fission-related genes DNM1L and MFF. An analysis of previously published gene expression datasets showed that high expression of MFF was significantly associated with poor prognosis in patients with AML. Based on this finding, we investigated the impact of mitochondrial dynamics in AML. Transduction of shRNA against fission-related genes, DNM1L and MFF, inhibited growth and increased the mitochondrial area in AML cell lines. Extracellular flux analysis showed that deletion of mitochondrial dynamic regulators reduced mitochondrial respiration without significantly affecting glycolysis, except in shDNM1L-transfected cells. Immunodeficient NOG mice transplanted with DNM1L- or MFF-knockdown AML cells survived significantly longer than controls. Treatment of AML cell lines with Mdivi-1, which inhibits the DRP1 encoded by DNM1L, inhibited cell proliferation and oxidative phosphorylation. Our results show that mitochondrial dynamics play an important role in AML, and provide novel biological insights. The inhibition of mitochondrial dynamics induces unique mitochondrial alterations, which may be explored as a potential therapeutic target in AML.

Indexed as

DynaminsGTP PhosphohydrolasesLeukemia, Myeloid, AcuteMitochondrial DynamicsMitochondrial ProteinsOxidative PhosphorylationAnimalsCell Line, TumorCell ProliferationHumansMembrane ProteinsMiceMitochondriaMolecular Targeted TherapyQuinazolinones3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinoneDNM1L protein, humanDynaminsGTP PhosphohydrolasesMembrane ProteinsMff protein, humanMitochondrial ProteinsQuinazolinonesAMLDNM1LMdivi-1MFFMitochondrial dynamics

Identifiers

PMID39283580

What Socratic holds

Textmetadata
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.