Evidence map›Paper›PMID 34686664›Full record

ArticleNature communications2021

Targeting miR-126 in inv(16) acute myeloid leukemia inhibits leukemia development and leukemia stem cell maintenance.

Lianjun Zhang, Le Xuan Truong Nguyen, Ying-Chieh Chen, Dijiong Wu, Guerry J Cook, Dinh Hoa Hoang, Casey J Brewer, Xin He, Haojie Dong, Shu Li and 15 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.2field-weighted citation impact, top 6% 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

38 citing papers in PubMed, 55 citations in OpenAlex.

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  11. Clinical applications of oligonucleotides for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  12. RNA mCell investigation · 2025
    Article
  13. Article
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  15. Review
  16. Article
  17. Review
  18. Metabolic dependencies of acute myeloid leukemia stem cells.International journal of hematology · 2024
    Review
  19. Article
  20. 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

25 authors at 4 institutions in 2 countries.

Lianjun Zhang *Gehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Le Xuan Truong Nguyen *Gehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Ying-Chieh ChenGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Dijiong WuDepartment of Hematology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310006, China.ORCID 0000-0003-2338-9365
Guerry J CookGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Dinh Hoa HoangGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Casey J BrewerGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Xin HeGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Haojie DongGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Shu LiDepartment of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.
Man LiGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Dandan ZhaoGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Jing QiGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Wei-Kai HuaGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Qi CaiGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Emily CarnahanGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Wei ChenIntegrated Genomics Core, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Xiwei WuIntegrated Genomics Core, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Piotr SwiderskiDepartment of Molecular Medicine, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Russell C RockneDepartment of Computational and Quantitative Medicine, Division of Mathematical Oncology, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.ORCID 0000-0002-1557-159X
Marcin KortylewskiDepartment of Immuno-oncology, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.ORCID 0000-0002-6003-1816
Ling LiGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
Bin ZhangGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.ORCID 0000-0003-4703-7524
Guido MarcucciGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.ORCID 0000-0002-3983-5908
Ya-Huei KuoGehr Family Center for Leukemia Research, Department of Hematological Malignancies Translational Science, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA. YKuo@coh.org.ORCID 0000-0003-2595-0419
City of Hope · USCity Of Hope National Medical Center · USSecond Affiliated Hospital of Zhejiang University · CNZhejiang Chinese Medical University · CN

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI XIWEI WU · 1985 to 2026
$86.3M
Targeting MicroRNAs to Eradicate Leukemia Stem CellsR01CA205247 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI KUO, YA-HUEI, MARCUCCI, GUIDO · 2017 to 2025
$4.8M
Information flow and state transitions at the system and multi-dimensional scales in leukemia progressionU01CA250046 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI KUO, YA-HUEI, MARCUCCI, GUIDO · 2020 to 2024
$3.6M
Vascular Remodeling in the Bone Marrow Leukemic Niche: A Therapeutic Target?R01CA248475 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI MARCUCCI, GUIDO, ZHANG, BIN · 2020 to 2024
$2.5M
Targeting Transcriptional Regulators for Immunotherapy of Acute Myeloid LeukemiaR01CA213131 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI KORTYLEWSKI, MARCIN · 2017 to 2021
$2.1M
NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA205247NCI NIH HHS R01 CA213131NCI NIH HHS R01 CA248475NCI NIH HHS U01 CA250046
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) harboring inv(16)(p13q22) expresses high levels of miR-126. Here we show that the CBFB-MYH11 (CM) fusion gene upregulates miR-126 expression through aberrant miR-126 transcription and perturbed miR-126 biogenesis via the HDAC8/RAN-XPO5-RCC1 axis. Aberrant miR-126 upregulation promotes survival of leukemia-initiating progenitors and is critical for initiating and maintaining CM-driven AML. We show that miR-126 enhances MYC activity through the SPRED1/PLK2-ERK-MYC axis. Notably, genetic deletion of miR-126 significantly reduces AML rate and extends survival in CM knock-in mice. Therapeutic depletion of miR-126 with an anti-miR-126 (miRisten) inhibits AML cell survival, reduces leukemia burden and leukemia stem cell (LSC) activity in inv(16) AML murine and xenograft models. The combination of miRisten with chemotherapy further enhances the anti-leukemia and anti-LSC activity. Overall, this study provides molecular insights for the mechanism and impact of miR-126 dysregulation in leukemogenesis and highlights the potential of miR-126 depletion as a therapeutic approach for inv(16) AML.

Indexed as

AnimalsAntineoplastic AgentsCalcium-Binding ProteinsCell Cycle ProteinsCell SurvivalChromosome InversionChromosomes, Human, Pair 16EGF Family of ProteinsGATA2 Transcription FactorGuanine Nucleotide Exchange FactorsHistone DeacetylasesHumansKaryopherinsLeukemia, Myeloid, AcuteMiceMicroRNAsAntineoplastic AgentsCalcium-Binding ProteinsCBFbeta-MYH11 fusion proteinCell Cycle ProteinsEGF Family of ProteinsEGFL7 protein, humanGATA2 protein, humanGATA2 Transcription FactorGuanine Nucleotide Exchange FactorsHDAC8 protein, humanHistone DeacetylasesKaryopherinsMicroRNAsMIRN126 microRNA, humanNuclear ProteinsOncogene Proteins, Fusionran GTP-Binding ProteinRAN protein, humanRCC1 protein, humanRepressor ProteinsXPO5 protein, human

Identifiers

PMID34686664
PMCPMC8536759
OpenAlexW3207807551

What OpenQuestion holds

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LicenceCC BY
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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.