ArticleNature medicine2018
Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia.
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Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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108citing papers in PubMed
11.6field-weighted citation impact, top 1% of its field
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Who cites it
108 citing papers in PubMed, 156 citations in OpenAlex.
- Understanding drug resistance in chronic myeloid leukemia through the lens of leukemic stem cell states: insights from single-cell analyses.Haematologica · 2026Review
- The Role of MicroRNAs Carried by Extracellular Vesicles in Tumorigenesis Through Reprogramming the Mitochondrial Information Processing System.International journal of molecular sciences · 2026Review
- Loss of endothelial miR-126 drives age-related decline in hematopoiesis.Haematologica · 2026Article
- Roles of extracellular vesicles in the pathogenesis of chronic myeloid leukemia.Journal of physiology and biochemistry · 2026Review
- Allosteric inhibition of RAN decreases miR-126 biogenesis in endothelial cells and controls acute myeloid leukemia growth.Communications biology · 2026Article
- Overcoming vascular niche-mediated TKI resistance in acute myeloid leukemia through miR-126 inhibition.NPJ systems biology and applications · 2026Article
- Decoding Leukemic Stem Cells in AML: From Identification to Targeted Eradication.Diseases (Basel, Switzerland) · 2026Review
- Circulating extracellular vesicle-microRNAs (EV-miRNAs) in leukemias and related disorders.Frontiers in medicine · 2026Review
- Reflecting on 30 years of miRNA biology in malignant hematology: current challenges and future directions.Blood advances · 2025Review
- MicroRNA-142 improves IL1RAP CAR-T cell activity in acute myeloid leukemia.Journal of hematology & oncology · 2025Article
- Review
- The roles of non-coding RNAs (ncRNAs) in the function of leukemic stem cells (LSCs): a comprehensive review.Discover oncology · 2025Review
- Clinical applications of oligonucleotides for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Function of hematopoiesis and bone marrow niche in inflammation and non-hematopoietic diseases.Life medicine · 2025Review
- Targeting RNA modification and mitochondrial metabolism cross talk in leukemic stem cells with CDK7 inhibitor TGN-1062.Blood advances · 2025Article
- A Gremlin 1-expressing splenic niche cell population restrains chronic myeloid leukemia by antagonizing the BMP pathway.Nature cancer · 2025Article
- Unleashing the TLR9-driven multilineage differentiation of myeloid leukemia cellsMolecular therapy. Nucleic acids · 2025Article
- Review
- miR-142 deficit in T cells during blast crisis promotes chronic myeloid leukemia immune escape.Nature communications · 2025Article
- HoxBlinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98-rearranged leukemia.The Journal of clinical investigation · 2025Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
32 authors at 8 institutions in 4 countries.
Bin ZhangGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.ORCID 0000-0003-4703-7524
Le Xuan Truong NguyenGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Ling LiGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Dandan ZhaoGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Bijender KumarGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Herman WuGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Allen LinGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Francesca PellicanoPaul O' Gorman Leukemia Research Centre, College of Medical, Veterinary and Life Sciences, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
Lisa HopcroftPaul O' Gorman Leukemia Research Centre, College of Medical, Veterinary and Life Sciences, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.ORCID 0000-0002-7022-1322
Yu-Lin SuDepartment of Immuno-oncology, City of Hope Medical Center, Duarte, California, USA.
Mhairi CoplandPaul O' Gorman Leukemia Research Centre, College of Medical, Veterinary and Life Sciences, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
Tessa L HolyoakePaul O' Gorman Leukemia Research Centre, College of Medical, Veterinary and Life Sciences, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
Calvin J KuoStanford University School of Medicine, Stanford, California, USA.
Ravi BhatiaUniversity of Alabama at Birmingham, Birmingham, Alabama, USA.
David S SnyderGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Haris AliGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Anthony S SteinGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Casey BrewerGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Huafeng WangGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Tinisha McDonaldGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Piotr SwiderskiGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Estelle TroadecGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Ching-Cheng ChenGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Adrienne DorranceDivision of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio, USA.
Vinod PullarkatGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Yate-Ching YuanGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Danilo PerrottiDepartment of Medicine, Biochemistry and Molecular Biology and the Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine Baltimore, Baltimore, Maryland, USA.
Nadia CarlessoGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Stephen J FormanGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
Marcin KortylewskiDepartment of Immuno-oncology, City of Hope Medical Center, Duarte, California, USA.ORCID 0000-0002-6003-1816
Ya-Huei KuoGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.ORCID 0000-0003-2595-0419
Guido MarcucciGehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope Medical Center, Duarte, California, USA.
City of Hope · USUniversity of Glasgow · GBCity Of Hope National Medical Center · USStanford University · USThe Ohio State University · USUniversity Medical Center HCMC · VNUniversity of Alabama at Birmingham · USUniversity of Maryland, Baltimore · US
Funding
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3MTransgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3MTargeting MicroRNAs to Eradicate Leukemia Stem CellsR01CA205247 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI KUO, YA-HUEI, MARCUCCI, GUIDO · 2017 to 2025
$4.8MPHARMACOLOGICAL MODULATION OF EPIGENETIC CHANTGES IN AMLR01CA102031 · NCI · OHIO STATE UNIVERSITY · PI GUZMAN, MONICA L, MARCUCCI, GUIDO · 2004 to 2017
$3.8MITSC for Leukemia: Novel Molecular Strategies for NCTN: "Individualized" TherapieU10CA180861 · NCI · OHIO STATE UNIVERSITY · PI BLOOMFIELD, CLARA D, MARCUCCI, GUIDO · 2014 to 2018
$3.4MMicroenvironmental Regulation of Leukemia Stem CellsR01CA172447 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BHATIA, RAVI · 2013 to 2023
$3.4MBiologic and Therapeutic Significance of miR-155 in AMLR01CA201184 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CROCE, CARLO M, GARZON, RAMIRO · 2016 to 2020
$2.7MTargeting Transcriptional Regulators for Immunotherapy of Acute Myeloid LeukemiaR01CA213131 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI KORTYLEWSKI, MARCIN · 2017 to 2021
$2.1MPhysiologic Regulation of Hematopoiesis by NotchR01DK097837 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI CARLESSO, NADIA · 2014 to 2017
$1.6MRole of microRNAs in the regulation of CML stem cell survival and self renewalR01CA163800 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI PERROTTI, DANILO · 2012 to 2017
$1.6MTargeting the aberrant kinome-epigenome in AMLR01CA158350 · NCI · OHIO STATE UNIVERSITY · PI GARZON, RAMIRO, MARCUCCI, GUIDO · 2012 to 2016
$1.5MResearch career advancement: Role of the SIRT1 deacetylase in maintenance of FLT3R00CA184411 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI LI, LING · 2015 to 2017
$747kCancer Research UK 11008NCI NIH HHS K99 CA184411NCI NIH HHS P30 CA016058NCI NIH HHS P30 CA033572NCI NIH HHS R00 CA184411NCI NIH HHS R01 CA102031NCI NIH HHS R01 CA158350NCI NIH HHS R01 CA163800NCI NIH HHS R01 CA172447NCI NIH HHS R01 CA201184NCI NIH HHS R01 CA205247NCI NIH HHS R01 CA213131NCI NIH HHS U10 CA180861NIDDK NIH HHS R01 DK097837
Abstract
Leukemia stem cells (LSCs) in individuals with chronic myelogenous leukemia (CML) (hereafter referred to as CML LSCs) are responsible for initiating and maintaining clonal hematopoiesis. These cells persist in the bone marrow (BM) despite effective inhibition of BCR-ABL kinase activity by tyrosine kinase inhibitors (TKIs). Here we show that although the microRNA (miRNA) miR-126 supported the quiescence, self-renewal and engraftment capacity of CML LSCs, miR-126 levels were lower in CML LSCs than in long-term hematopoietic stem cells (LT-HSCs) from healthy individuals. Downregulation of miR-126 levels in CML LSCs was due to phosphorylation of Sprouty-related EVH1-domain-containing 1 (SPRED1) by BCR-ABL, which led to inhibition of the RAN-exportin-5-RCC1 complex that mediates miRNA maturation. Endothelial cells (ECs) in the BM supply miR-126 to CML LSCs to support quiescence and leukemia growth, as shown using mouse models of CML in which Mir126a (encoding miR-126) was conditionally knocked out in ECs and/or LSCs. Inhibition of BCR-ABL by TKI treatment caused an undesired increase in endogenous miR-126 levels, which enhanced LSC quiescence and persistence. Mir126a knockout in LSCs and/or ECs, or treatment with a miR-126 inhibitor that targets miR-126 expression in both LSCs and ECs, enhanced the in vivo anti-leukemic effects of TKI treatment and strongly diminished LSC leukemia-initiating capacity, providing a new strategy for the elimination of LSCs in individuals with CML.
Indexed as
Cell Self RenewalStem Cell NicheAnimalsBone MarrowDown-RegulationEndothelial CellsExtracellular VesiclesFusion Proteins, bcr-ablGene Expression Regulation, LeukemicGene Knockdown TechniquesGene SilencingHematopoietic Stem CellsHumansLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMiceMicroRNAsFusion Proteins, bcr-ablMicroRNAsMIRN126 microRNA, humanProtein Kinase Inhibitors
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