Evidence map›Paper›PMID 22932801›Full record

ArticleBlood2012

Massive evolution of the immunoglobulin heavy chain locus in children with B precursor acute lymphoblastic leukemia.

Charles Gawad, Francois Pepin, Victoria E H Carlton, Mark Klinger, Aaron C Logan, David B Miklos, Malek Faham, Gary Dahl, Norman Lacayo

Abstract read
In one paragraph

Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
12.6field-weighted citation impact, top 1% 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

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.

  1. Pooled it
  2. Next-Generation Sequencing in Adult B Cell Acute Lymphoblastic Leukemia Patients.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2017
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7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Charles GawadDivision of Hematology-Oncology-Stem Cell Transplantation and Cancer Biology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. cgawad@stanford.edu
Francois Pepin
Victoria E H Carlton
Mark Klinger
Aaron C Logan
David B Miklos
Malek Faham
Gary Dahl
Norman Lacayo
Cancer Prevention Institute of California · USStanford University · USStanford Cancer Institute

Funding

TUMOR SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN BONE MARROW TRANSPLANTATIONP01CA049605 · NCI · STANFORD UNIVERSITY · PI David B. Miklos · 1989 to 2026
$73.3M
NCI NIH HHS P01 CA049605
6 · The paper itself

Abstract

The ability to distinguish clonal B-cell populations based on the sequence of their rearranged immunoglobulin heavy chain (IgH) locus is an important tool for diagnosing B-cell neoplasms and monitoring treatment response. Leukemic precursor B cells may continue to undergo recombination of the IgH gene after malignant transformation; however, the magnitude of evolution at the IgH locus is currently unknown. We used next-generation sequencing to characterize the repertoire of IgH sequences in diagnostic samples of 51 children with B precursor acute lymphoblastic leukemia (B-ALL). We identified clonal IgH rearrangements in 43 of 51 (84%) cases and found that the number of evolved IgH sequences per patient ranged dramatically from 0 to 4024. We demonstrate that the evolved IgH sequences are not the result of amplification artifacts and are unique to leukemic precursor B cells. In addition, the evolution often follows an allelic exclusion pattern, where only 1 of 2 rearranged IgH loci exhibit ongoing recombination. Thus, precursor B-cell leukemias maintain evolution at the IgH locus at levels that were previously underappreciated. This finding sheds light on the mechanisms associated with leukemic clonal evolution and may fundamentally change approaches for monitoring minimal residual disease burden.

Indexed as

Genetic LociAge FactorsAlgorithmsBone MarrowCase-Control StudiesChildChild, PreschoolClonal EvolutionDNA Mutational AnalysisGenes, Immunoglobulin Heavy ChainHumansInfantInfant, NewbornPrecursor B-Cell Lymphoblastic Leukemia-LymphomaRecurrenceValidation Studies as Topic

Identifiers

PMID22932801
PMCPMC3507147
OpenAlexW1972308638

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.