Evidence map›Paper›PMID 37986825›Full record

ArticleResearch square2023

Mutation order in acute myeloid leukemia identifies uncommon patterns of evolution and illuminates phenotypic heterogeneity.

Matthew Schwede, Katharina Jahn, Jack Kuipers, Linde A Miles, Robert L Bowman, Troy Robinson, Ken Furudate, Hidetaka Uryu, Tomoyuki Tanaka, Yuya Sasaki and 7 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 4 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 7 institutions in 5 countries.

Matthew SchwedeDepartment of Medicine, Division of Hematology, Stanford University, Stanford, CA, USA.ORCID https://orcid.org/0000-0002-0778-9230
Katharina JahnBiomedical Data Science, Institute for Computer Science, Free University of Berlin, Berlin, Germany.
Jack KuipersDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Linde A MilesDivision of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Robert L BowmanDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Troy RobinsonHuman Oncology and Pathogenesis Program, Molecular Cancer Medicine Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Ken FurudateDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID https://orcid.org/0000-0003-1272-5490
Hidetaka UryuDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID https://orcid.org/0000-0001-7167-895X
Tomoyuki TanakaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Yuya SasakiDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID https://orcid.org/0000-0001-8232-0910
Asiri EdiriwickremaDepartment of Medicine, Division of Hematology, Stanford University, Stanford, CA, USA.ORCID https://orcid.org/0000-0002-6480-8290
Brooks BenardDepartment of Pathology, Stanford University, Stanford, CA, USA.ORCID https://orcid.org/0000-0001-7154-744X
Andrew J GentlesDepartment of Biomedical Data Science, Stanford University, School of Medicine, Stanford, California, USA.ORCID https://orcid.org/0000-0002-0941-9858
Ross LevineHuman Oncology and Pathogenesis Program, Molecular Cancer Medicine Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.ORCID https://orcid.org/0000-0002-7884-1905
Niko BeerenwinkelDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Koichi TakahashiDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.ORCID https://orcid.org/0000-0002-8027-9659
Ravindra MajetiDepartment of Medicine, Division of Hematology, Stanford University, Stanford, CA, USA.ORCID https://orcid.org/0000-0002-5814-0984
The University of Texas MD Anderson Cancer Center · USSIB Swiss Institute of Bioinformatics · CHStanford University · USCalifornia Institute for Regenerative Medicine · USMemorial Sloan Kettering Cancer Center · USCalifornia University of Pennsylvania · USCincinnati Children's Hospital Medical Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
POSTDOCTORAL TRAINING IN MEDICAL INFORMATION SCIENCEST15LM007033 · NLM · STANFORD UNIVERSITY · PI SYLVIA KATINA PLEVRITIS · 1985 to 2026
$25.5M
Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
Synergistic role of signaling and epigenetics in leukemic transformationR35CA197594 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Ross L Levine · 2017 to 2026
$11.4M
Human Acute Myeloid Leukemia Stem CellsR01CA251331 · NCI · STANFORD UNIVERSITY · PI MAJETI, RAVINDRA · 2020 to 2024
$1.8M
Interrogating oncogene-dependency and mutation order in FLT3 mutant AMLR00CA248460 · NCI · UNIVERSITY OF PENNSYLVANIA · PI BOWMAN, ROBERT LYLE · 2022 to 2024
$743k
Dissecting the role of clonal evolution in NPM1-mutant AMLR00CA252005 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI MILES, LINDE A · 2022 to 2024
$669k
Single cell characterization of human acute myeloid leukemiaF32CA250304 · NCI · STANFORD UNIVERSITY · PI EDIRIWICKREMA, ASIRI · 2020 to 2022
$254k
NCI NIH HHS F32 CA250304NCI NIH HHS P30 CA008748NCI NIH HHS R00 CA248460NCI NIH HHS R00 CA252005NCI NIH HHS R01 CA251331NCI NIH HHS R35 CA197594NCI NIH HHS T32 CA009302NLM NIH HHS T15 LM007033
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) has a poor prognosis and a heterogeneous mutation landscape. Although common mutations are well-studied, little research has characterized how the sequence of mutations relates to clinical features. Using published, single-cell DNA sequencing data from three institutions, we compared clonal evolution patterns in AML to patient characteristics, disease phenotype, and outcomes. Mutation trees, which represent the order of select mutations, were created for 207 patients from targeted panel sequencing data using 1 639 162 cells, 823 mutations, and 275 samples. In 224 distinct orderings of mutated genes, mutations related to DNA methylation typically preceded those related to cell signaling, but signaling-first cases did occur, and had higher peripheral cell counts, increased signaling mutation homozygosity, and younger patient age. Serial sample analysis suggested that

Identifiers

PMID37986825
PMCPMC10659552
OpenAlexW4388408386

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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.