Evidence map›Paper›PMID 22160699›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

High-throughput VDJ sequencing for quantification of minimal residual disease in chronic lymphocytic leukemia and immune reconstitution assessment.

Aaron C Logan, Hong Gao, Chunlin Wang, Bita Sahaf, Carol D Jones, Eleanor L Marshall, Ismael Buño, Randall Armstrong, Andrew Z Fire, Kenneth I Weinberg and 6 more

Open access · bronzeAbstract readEvaluation Study
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
8.2field-weighted citation impact, top 2% 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

87 citing papers in PubMed, 171 citations in OpenAlex.

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  9. MRD-directed therapy in CLL: ready for prime time?Hematology. American Society of Hematology. Education Program · 2023
    Review
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27 more citing papers are in PubMed but not listed here.

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

16 authors at 5 institutions in 2 countries.

Aaron C LoganDivisions of Blood and Marrow Transplantation and Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hong Gao
Chunlin Wang
Bita Sahaf
Carol D Jones
Eleanor L Marshall
Ismael Buño
Randall Armstrong
Andrew Z Fire
Kenneth I Weinberg
Michael Mindrinos
James L Zehnder
Scott D Boyd
Wenzhong Xiao
Ronald W Davis
David B Miklos
New York Genome Center · USNational Marrow Donor Program · USHospital General Universitario Gregorio Marañón · ESStanford Health Care · USStanford University · US

Funding

WHOLE YEAST GENOME TRANSCRIPTIONAL AND FUNCTIONAL GENE MAPS--A FEASIBILITY STUDYP01HG000205 · NHGRI · STANFORD UNIVERSITY · PI DAVIS, RONALD WAYNE, HOWE, ROGER THOMAS · 1990 to 2016
$120.9M
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 CA049605NHGRI NIH HHS P01 HG000205
6 · The paper itself

Abstract

The primary cause of poor outcome following allogeneic hematopoietic cell transplantation (HCT) for chronic lymphocytic leukemia (CLL) is disease recurrence. Detection of increasing minimal residual disease (MRD) following HCT may permit early intervention to prevent clinical relapse; however, MRD quantification remains an uncommon diagnostic test because of logistical and financial barriers to widespread use. Here we describe a method for quantifying CLL MRD using widely available consensus primers for amplification of all Ig heavy chain (IGH) genes in a mixture of peripheral blood mononuclear cells, followed by high-throughput sequencing (HTS) for disease-specific IGH sequence quantification. To achieve accurate MRD quantification, we developed a systematic bioinformatic methodology to aggregate cancer clone sequence variants arising from systematic and random artifacts occurring during IGH-HTS. We then compared the sensitivity of IGH-HTS, flow cytometry, and allele-specific oligonucleotide PCR for MRD quantification in 28 samples collected from 6 CLL patients following allogeneic HCT. Using amplimer libraries generated with consensus primers from patient blood samples, we demonstrate the sensitivity of IGH-HTS with 454 pyrosequencing to be 10(-5), with a high correlation between quantification by allele-specific oligonucleotide PCR and IGH-HTS (r = 0.85). From the same dataset used to quantify MRD, IGH-HTS also allowed us to profile IGH repertoire reconstitution after HCT-information not provided by the other MRD methods. IGH-HTS using consensus primers will broaden the availability of MRD quantification in CLL and other B cell malignancies, and this approach has potential for quantitative evaluation of immune diversification following transplant and nontransplant therapies.

Indexed as

Hematopoietic Stem Cell TransplantationTransplantation, HomologousComputational BiologyFlow CytometryHigh-Throughput Nucleotide SequencingHumansImmunoglobulin Heavy ChainsLeukemia, Lymphocytic, Chronic, B-CellNeoplasm, ResidualOligonucleotidesPolymerase Chain ReactionSecondary PreventionSensitivity and SpecificityImmunoglobulin Heavy ChainsOligonucleotides

Identifiers

PMID22160699
PMCPMC3248502
OpenAlexW2171240476

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.