ArticleNature genetics2015
The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Nature genetics, 2015. 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 300 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
300citing papers in PubMed, 1 pooled it
47.3field-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
300 citing papers in PubMed, 1 synthesis or guideline pooled it, 490 citations in OpenAlex.
- Survival outcomes in secondary and primary acute lymphoblastic leukemia: a systematic review and meta-analysis.Scientific reports · 2025Pooled it
- Bortezomib and vorinostat in combination with mitoxantrone, dexamethasone, and pegasparaginase during induction and reinduction for infants with acute lymphoblastic leukaemia: a multicentre single-arm phase 1/2 study.The Lancet. Haematology · 2026Trial
- Azacitidine as epigenetic priming for chemotherapy is safe and well-tolerated in infants with newly diagnosedHaematologica · 2024Trial
- Cytogenetic Diversity of Variant Philadelphia Translocations in Chronic Myeloid Leukemia.International journal of laboratory hematology · 2026Article
- The Fanconi anemia pathway restrains MLL-rearranged leukemogenesis through suppressing non-homologous end joining-mediated genomic instability.Nature communications · 2026Article
- Modeling constrained tumor evolution through hybrid Ornstein-Uhlenbeck and branching dynamics.iScience · 2026Article
- Antigen Pressure, Clonal Evolution, and Lineage Plasticity in B-Cell Acute Lymphoblastic Leukemia: Resistance Biology in the Immunotherapy Era.Current hematologic malignancy reports · 2026Review
- Review
- From cell lines to PDXs: in vivo confirmation of synergistic drug responses identified in leukemia cell line models.Blood neoplasia · 2026Article
- Article
- Combined inhibition of DOT1L and BCL-2 induces synergistic anti-leukemic effects in MLL-rearranged acute myeloid leukemia via suppression of the PI3K/AKT pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Article
- The hidden regulators: Non-coding RNAs in KMT2A-rearranged acute lymphoblastic leukemia.International journal of cancer · 2026Review
- An integrative molecular map of pediatric B-cell precursor acute lymphoblastic leukemia.Communications medicine · 2026Article
- Comparison of gene fusion detection algorithms reveals frequently overlooked driver fusions in hematologic malignancies.NPJ precision oncology · 2026Article
- A microRNA expression signature in infant t(4;11) KMT2A::AFF1+ BCP-ALL uncovers novel therapeutic targets.HemaSphere · 2026Article
- Article
- SKIDA1 sustains MLL::ENL-expressing hematopoietic progenitors during neonatal stages and promotes B-lineage priming.Blood neoplasia · 2026Article
- Pediatric leukemia: origins, pathogenesis, the role of microenvironment and immunological modulation.Frontiers in immunology · 2026Review
- Fetal context conveys heritable protection against MLL-rearranged AML that depends on MLL3.Blood · 2026Article
240 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
51 authors at 6 institutions in 3 countries.
Anna K Andersson1] Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Clinical Genetics, Lund University, Lund, Sweden.
Jing MaDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Jianmin WangDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Xiang ChenDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Amanda Larson GedmanDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Jinjun DangDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Joy NakitandweDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Linda HolmfeldtDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000000341403423
Matthew ParkerDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
John EastonPediatric Cancer Genome Project Laboratory, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Robert HuetherDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000000170777470
Richard KriwackiDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Michael RuschDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Gang WuDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000000216785864
Yongjin LiDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Heather MulderPediatric Cancer Genome Project Laboratory, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Susana RaimondiDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Stanley PoundsDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000000291672114
Guolian KangDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Lei ShiDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Jared BecksfortDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Pankaj GuptaDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Debbie Payne-TurnerDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Bhavin VadodariaPediatric Cancer Genome Project Laboratory, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Kristy BoggsPediatric Cancer Genome Project Laboratory, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Donald YergeauPediatric Cancer Genome Project Laboratory, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Jayanthi MannePediatric Cancer Genome Project Laboratory, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Guangchun SongDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Michael EdmonsonDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Panduka NagahawatteDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Lei WeiDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Cheng ChengDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Deqing PeiDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Rosemary SuttonChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia.
Nicola C VennChildren's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia.
Albert ChetcutiTumor Bank, Children's Cancer Research Unit, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
Amanda RushTumor Bank, Children's Cancer Research Unit, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
Daniel CatchpooleTumor Bank, Children's Cancer Research Unit, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
Jesper HeldrupDepartment of Pediatrics, Skåne University Hospital, Lund, Sweden.
Thoas FioretosDepartment of Clinical Genetics, Lund University, Lund, Sweden.
Charles Lu1] Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA. [2] Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Li Ding1] Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA. [2] Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Ching-Hon Pui1] Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Sheila ShurtleffDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Charles G MullighanDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000000218711850
Elaine R Mardis1] Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA. [2] Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Richard K Wilson1] Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA. [2] Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Tanja A Gruber1] Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Jinghui ZhangDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
James R DowningDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project
St. Jude Children's Research Hospital · USWashington University in St. Louis · USChildren's Hospital at Westmead · AUUNSW Sydney · AULund University · SESkåne University Hospital · SE
Funding
Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9MTwo-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Dean G. Tang · 1985 to 2026
$116.6MNCI NIH HHS P30 CA016056NCI NIH HHS P30 CA021765PHS HHS GSE64192
Abstract
Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL-R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10(-5)) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL, was rarely mutated in infant MLL-R ALL.
Indexed as
MutationAllelic ImbalanceCohort StudiesDNA Mutational AnalysisGene FrequencyHistone-Lysine N-MethyltransferaseHumansInfantMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, FusionPhosphatidylinositol 3-KinasesPrecursor Cell Lymphoblastic Leukemia-LymphomaProtein-Tyrosine Kinasesras ProteinsSignal TransductionHistone-Lysine N-MethyltransferaseKMT2A protein, humanMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, FusionPhosphatidylinositol 3-KinasesProtein-Tyrosine Kinasesras Proteins
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
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.