ArticleNature2018
The genetic basis and cell of origin of mixed phenotype acute leukaemia.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00137111 (Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia), which is not on this map. Cited by 205 papers.
0numbers the graph read from it
0cells of the map it votes in
205citing papers in PubMed
22.2field-weighted citation impact, top 1% of its field
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.
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.
Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Who cites it
205 citing papers in PubMed, 359 citations in OpenAlex.
- The association of complex genetic background with the prognosis of acute leukemia with ambiguous lineage.Scientific reports · 2021Trial
- Trial
- Trial
- Lineage switch in leukemia and lymphoma: case reports and molecular and cellular mechanisms.Blood neoplasia · 2026Review
- FUS controls muscle differentiation through phase separation-mediated recruitment of the transcription factors MEF2 and ETV5.The EMBO journal · 2026Article
- Plasticity under pressure: biology and detection of lineage switch in acute leukemia.Leukemia · 2026Review
- Article
- A genomic and epigenomic lens into the biology of acute lymphoblastic leukaemia.Nature reviews. Cancer · 2026Review
- Extensive binding of poorly characterized human transcription factors to genomic dark matter.Nature communications · 2026Article
- Co-option of lineage plasticity as a hallmark of multipotent acute leukemias.Blood neoplasia · 2026Review
- Pitfalls and Challenges in the Detection of ZNF384 Rearrangements by Fluorescence in Situ Hybridization.Genes, chromosomes & cancer · 2026Article
- Article
- Multi-omics analysis of pediatric minimally differentiated acute myeloid leukemia reveals RUNX1-driven stemness and chemoresistance.Leukemia · 2026Article
- Review
- Significance of Myelodysplasia-Related Mutations and the Genetic Landscape of Acute Leukemias of Ambiguous Lineage.International journal of laboratory hematology · 2026Review
- Article
- Acute leukemia of ambiguous lineage: the known and the uncertain.Haematologica · 2026Review
- Optical genome mapping reveals a recurrent translocation, t(14;16), in T/myeloid mixed phenotype acute leukemia: report of two cases.Molecular cytogenetics · 2026Article
- Immunophenotypically Defined Mixed-Phenotype Acute Leukemias: A Clinicopathologic Analysis of 52 Cases.EJHaem · 2026Article
- Multidimensional mapping of stimulation-responsive regulatory elements and candidate causal variants in T cell activation.Science advances · 2026Article
145 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
62 authors at 20 institutions in 13 countries.
Thomas B AlexanderDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Zhaohui GuDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Ilaria IacobucciDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Kirsten DickersonDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
John K ChoiDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Beisi XuDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Debbie Payne-TurnerDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Hiroki YoshiharaDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Mignon L LohDepartment of Pediatrics, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.
John HoranAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA.
Barbara BuldiniDepartment of Women and Child Health, Hemato-Oncology Division, University of Padova, Padova, Italy.
Giuseppe BassoDepartment of Women and Child Health, Hemato-Oncology Division, University of Padova, Padova, Italy.
Sarah ElitzurPediatric Hematology-Oncology, Schneider Children's Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Valerie de HaasPrinses Maxima Centre, Utrecht, The Netherlands.
C Michel ZwaanPrinses Maxima Centre, Utrecht, The Netherlands.
Allen YeohDepartment of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Dirk ReinhardtUniversitäts-Klinikum, Essen, Germany.
Daisuke TomizawaDivision of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
Nobutaka KiyokawaDepartment of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.
Tim LammensDepartment of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
Barbara De MoerlooseDepartment of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
Daniel CatchpooleThe Tumour Bank CCRU, The Kids Research Institute, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
Hiroki HoriDepartment of Pediatrics, Mie University, Tsu, Japan.
Anthony MoormanWolfson Childhood Cancer Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK.
Andrew S MooreThe University of Queensland Diamantina Institute & Children's Health, Brisbane, Queensland, Australia.
Ondrej HrusakDepartment of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
Soheil MeshinchiFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA.
Etan OrgelChildren's Center for Cancer and Blood Disease, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Meenakshi DevidasUniversity of Florida, Gainesville, FL, USA.
Michael BorowitzJohns Hopkins Medical Institutions, Baltimore, MD, USA.
Brent WoodUniversity of Washington, Seattle, WA, USA.
Nyla A HeeremaThe Ohio State University School of Medicine, Columbus, OH, USA.
Andrew CarrolUniversity of Alabama at Birmingham, Birmingham, AL, USA.
Yung-Li YangDepartment of Laboratory Medicine and Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Malcolm A SmithCancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA.
Tanja M DavidsenCenter for Biomedical Informatics and Information Technology, National Cancer Institute, Rockville, MD, USA.
Leandro C HermidaOffice of Cancer Genomics, National Cancer Institute, Bethesda, MD, USA.
Patee GesuwanOffice of Cancer Genomics, National Cancer Institute, Bethesda, MD, USA.
Marco A MarraMichael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
Yussanne MaMichael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
Andrew J MungallMichael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
Richard A MooreMichael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
Steven J M JonesMichael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
Marcus ValentineCytogenetics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN, USA.
Laura J JankeDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Jeffrey E RubnitzDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Ching-Hon PuiDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Liang DingDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Yu LiuDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Jinghui ZhangDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Kim E NicholsDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
James R DowningDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Xueyuan CaoDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Lei ShiDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Stanley PoundsDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Scott NewmanDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Deqing PeiDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Jaime M Guidry AuvilOffice of Cancer Genomics, National Cancer Institute, Bethesda, MD, USA.
Daniela S GerhardOffice of Cancer Genomics, National Cancer Institute, Bethesda, MD, USA.
Stephen P HungerDivision of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Hiroto InabaDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA. hiroto.inaba@stjude.org.
Charles G MullighanDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA. charles.mullighan@stjude.org.
St. Jude Children's Research Hospital · USNational Cancer Institute · USBC Cancer Agency · CACanada's Michael Smith Genome Sciences Centre · CAGhent University Hospital · BENational Center For Child Health and Development · JPPrincess Máxima Center · NLUniversity of Padua · ITArcadia · USCharles University · CZChildren's Hospital at Westmead · AUChildren's Hospital of Los Angeles · USChildren's Hospital of Philadelphia · USEmory University · USEssen University Hospital · DEJohns Hopkins University · USMie University · JPNational Taiwan University Hospital · TWNational University of Singapore · SGNewcastle University · GB
Funding
NCTN BIQSFP ANBL1531 (NRT)U10CA180886 · NCI · PUBLIC HEALTH INSTITUTE · PI Douglas S. Hawkins · 2014 to 2026
$390.6MViral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9MCOG SDMC - Statistics CoreU10CA180899 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TODD A ALONZO · 2014 to 2026
$132.8MChildren's Oncology Group Statistics &Data Center GrantU10CA098413 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI ANDERSON, JAMES R · 2003 to 2013
$67.5MCPML - Project 3: Genome-wide Studies of Adverse EffectsP50GM115279 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI RELLING, MARY V · 2015 to 2019
$15.1MSupport for Human Specimen Banking in NCI-Supported Cancer Clinical TrialsU24CA114766 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI RAMIREZ MILAN, NILSA DEL CARMEN · 2005 to 2014
$14.5MTranslating genomic discoveries to improved outcomes for high risk acute leukemiaR35CA197695 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Charles G Mullighan · 2017 to 2026
$11.4MBiology/prognostic implications of Flt3 mutations in AMLR01CA114563 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI MESHINCHI, SOHEIL · 2005 to 2016
$4.4MNCI NIH HHS P30 CA021765NCI NIH HHS R01 CA114563NCI NIH HHS R35 CA197695NCI NIH HHS U10 CA098413NCI NIH HHS U10 CA180886NCI NIH HHS U10 CA180899NCI NIH HHS U24 CA114766NIGMS NIH HHS P50 GM115279
Abstract
Mixed phenotype acute leukaemia (MPAL) is a high-risk subtype of leukaemia with myeloid and lymphoid features, limited genetic characterization, and a lack of consensus regarding appropriate therapy. Here we show that the two principal subtypes of MPAL, T/myeloid (T/M) and B/myeloid (B/M), are genetically distinct. Rearrangement of ZNF384 is common in B/M MPAL, and biallelic WT1 alterations are common in T/M MPAL, which shares genomic features with early T-cell precursor acute lymphoblastic leukaemia. We show that the intratumoral immunophenotypic heterogeneity characteristic of MPAL is independent of somatic genetic variation, that founding lesions arise in primitive haematopoietic progenitors, and that individual phenotypic subpopulations can reconstitute the immunophenotypic diversity in vivo. These findings indicate that the cell of origin and founding lesions, rather than an accumulation of distinct genomic alterations, prime tumour cells for lineage promiscuity. Moreover, these findings position MPAL in the spectrum of immature leukaemias and provide a genetically informed framework for future clinical trials of potential treatments for MPAL.
Indexed as
Cell LineageDNA Mutational AnalysisFemaleGenetic VariationGenome, HumanGenomicsHumansImmunophenotypingLeukemia, Biphenotypic, AcuteMaleModels, GeneticMutationNeoplastic Stem CellsPhenotypeTrans-ActivatorsTrans-ActivatorsZNF384 protein, human
Identifiers
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Read underepoch 390
Registered trials
NCT00137111ClinicalTrials.gov
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.