Evidence map›Paper›PMID 23748046›Full record

ArticleMutation research2013

The rate of spontaneous mutations in human myeloid cells.

David J Araten, Ondrej Krejci, Kimberly Ditata, Mark Wunderlich, Katie J Sanders, Leah Zamechek, James C Mulloy

Abstract read
In one paragraph

Article in Mutation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

7 citing papers in PubMed, 16 citations in OpenAlex.

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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

7 authors at 3 institutions in 1 country.

David J AratenDivision of Hematology, Department of Veterans Affairs New York Harbor Healthcare System, United States; Division of Hematology, Department of Medicine, NYU School of Medicine and the NYU Langone Cancer Center, United States. Electronic address: david.araten@nyumc.org.
Ondrej Krejci
Kimberly Ditata
Mark Wunderlich
Katie J Sanders
Leah Zamechek
James C Mulloy
Cincinnati Children's Hospital Medical Center · USNYU Langone’s Laura and Isaac Perlmutter Cancer CenterNYU Langone Health · US

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MARK Reid PHILIPS · 1985 to 2026
$83.1M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR026314 · NCRR · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E. · 2009 to 2011
$14.3M
Cincinnati Center for Excellence in Molecular HematologyP30DK090971 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI ZHENG, YI · 2010 to 2015
$4.0M
Measurement &modulation of the mutation rate in humansR01CA109258 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI ARATEN, DAVID J. · 2004 to 2007
$1.1M
Genomic Instability in Ageing and CancerI01BX000670 · VA · VA MEDICAL CENTER · PI ARATEN, DAVID J. · 2009 to 2013
–
BLRD VA I01 BX000670NCI NIH HHS 5P30CA016087-33NCI NIH HHS P30 CA016087NCI NIH HHS R01 CA109258NCI NIH HHS R01-CA109258NCRR NIH HHS 1UL1RR026314-01NCRR NIH HHS UL1 RR026314NIDDK NIH HHS DK090971NIDDK NIH HHS P30 DK090971
6 · The paper itself

Abstract

The mutation rate (μ) is likely to be a key parameter in leukemogenesis, but historically, it has been difficult to measure in humans. The PIG-A gene has some advantages for the detection of spontaneous mutations because it is X-linked, and therefore only one mutation is required to disrupt its function. Furthermore, the PIG-A-null phenotype is readily detected by flow cytometry. Using PIG-A, we have now provided the first in vitro measurement of μ in myeloid cells, using cultures of CD34+ cells that are transduced with either the AML-ETO or the MLL-AF9 fusion genes and expanded with cytokines. For the AML-ETO cultures, the median μ value was ∼9.4×10(-7) (range ∼3.6-23×10(-7)) per cell division. In contrast, few spontaneous mutations were observed in the MLL-AF9 cultures. Knockdown of p53 or introduction of mutant NRAS or FLT3 alleles did not have much of an effect on μ. Based on these data, we provide a model to predict whether hypermutability must occur in the process of leukemogenesis.

Indexed as

Mutation RateCells, CulturedCell Transformation, NeoplasticCore Binding Factor Alpha 2 SubunitFetal BloodFlow CytometryGene Knockdown TechniquesGenes, p53GlycosylphosphatidylinositolsHumansMembrane ProteinsMutationMyeloid CellsMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, FusionRUNX1 Translocation Partner 1 ProteinAML1-ETO fusion protein, humanCore Binding Factor Alpha 2 SubunitGlycosylphosphatidylinositolsMembrane ProteinsMLL-AF9 fusion protein, humanMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, Fusionphosphatidylinositol glycan-class A proteinRUNX1 Translocation Partner 1 Proteinacute myelogenous leukemiaAMLBLCLsB-lymphoblastoid cell linesglycosylphosphatidylinositolGPIGPI-linked proteinsHuman myeloid culturesMutation rateMyeloid leukemia.paroxysmal nocturnal hemoglobinuriaPIG-A genePNHSpontaneous somatic mutations

Identifiers

PMID23748046
PMCPMC4524336
OpenAlexW2063885483

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.