Evidence map›Paper›PMID 34092057›Full record

ArticleHaematologica2022

IGHV-associated methylation signatures more accurately predict clinical outcomes of chronic lymphocytic leukemia patients than IGHV mutation load.

Dianna Hussmann, Anna Starnawska, Louise Kristensen, Iben Daugaard, Astrid Thomsen, Tina E Kjeldsen, Christine Søholm Hansen, Jonas Bybjerg-Grauholm, Karina Dalsgaard Johansen, Maja Ludvigsen and 6 more

Open access · goldAbstract read
In one paragraph

Article in Haematologica, 2022. 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
0.9field-weighted citation impact, top 25% 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, 9 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

16 authors at 5 institutions in 2 countries.

Dianna HussmannDepartment of Biomedicine, Aarhus University, Aarhus.
Anna StarnawskaDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark; Centre for Genomics and Personalized Medicine, CGPM, Aarhus University, Aarhus.
Louise KristensenDepartment of Pathology, Odense University Hospital, Odense.
Iben DaugaardDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Pathology, Aarhus University Hospital, Aarhus.
Astrid ThomsenDepartment of Biomedicine, Aarhus University, Aarhus.
Tina E KjeldsenDepartment of Biomedicine, Aarhus University, Aarhus.
Christine Søholm HansenThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Department for Congenital Disorders, Statens Serum Institut, Copenhagen.
Jonas Bybjerg-GrauholmThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Department for Congenital Disorders, Statens Serum Institut, Copenhagen.
Karina Dalsgaard JohansenDepartment of Hematology, Aarhus University Hospital, Aarhus.
Maja LudvigsenDepartment of Hematology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus.
Thomas KristensenDepartment of Pathology, Odense University Hospital, Odense.
Thomas Stauffer LarsenDepartment of Haematology, Odense University Hospital, Odense.
Michael Boe MøllerDepartment of Pathology, Odense University Hospital, Odense.
Charlotte Guldborg NyvoldHaematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, Odense.
Lise Lotte HansenDepartment of Biomedicine, Aarhus University, Aarhus.
Tomasz K WojdaczDepartment of Biomedicine, Aarhus University, Aarhus, Denmark; Aarhus Institute of Advanced Studies, Aarhus University, Aarhus, Denmark; Independent Clinical Epigenetics Laboratory, Pomeranian Medical University, Szczecin. tomasz.wojdacz@pum.edu.pl.
Aarhus University · DKOdense University Hospital · DKAarhus University Hospital · DKLundbeck Foundation · DKPomeranian Medical University · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Currently, no molecular biomarker indices are used in standard care to make treatment decisions at diagnosis of chronic lymphocytic leukemia (CLL). We used Infinium MethylationEPIC array data from diagnostic blood samples of 114 CLL patients and developed a procedure to stratify patients based on methylation signatures associated with mutation load of the IGHV gene. This procedure allowed us to predict the time to treatment with a hazard ratio (HR) of 8.34 (95% confidence interval [CI]: 4.54-15.30), as opposed to a HR of 4.35 (95% CI: 2.60-7.28) using IGHV mutation status. Detailed evaluation of 17 cases for which the two classification procedures gave discrepant results showed that these cases were incorrectly classified using IGHV status. Moreover, methylation-based classification stratified patients with different overall survival (HR=1.82; 95% CI: 1.07-3.09), which was not possible using IGHV status. Furthermore, we assessed the performance of the developed classification procedure using published HumanMethylation450 array data for 159 patients for whom information on time to treatment, overall survival and relapse was available. Despite 450K array methylation data not containing all the biomarkers used in our classification procedure, methylation signatures again stratified patients with significantly better accuracy than did IGHV mutation load regarding all available clinical outcomes. Thus, stratification using IGHV-associated methylation signatures may provide better prognostic power than IGHV mutation status.

Indexed as

Leukemia, Lymphocytic, Chronic, B-CellHumansImmunoglobulin Heavy ChainsMethylationMutationPrognosisImmunoglobulin Heavy Chains

Identifiers

PMID34092057
PMCPMC8968906
OpenAlexW3171224028

What OpenQuestion holds

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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.