ArticleLeukemia2023
Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY.
Erratum issued Registry-linked trialOpen access · hybridAbstract read
In one paragraph
Article in Leukemia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT07499635 (Immunophenotypic Evaluation of Inhibitory Immune Receptors CD305 and CD85d in B-Cell Lymphoid Neoplasms), which is not on this map. Cited by 32 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
7.2field-weighted citation impact, top 2% of its field
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.
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.
Immunophenotypic Evaluation of Inhibitory Immune Receptors CD305 and CD85d in B-Cell Lymphoid Neoplasms
Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- Identification of 4 autophagy-related genetic variants as risk factors for chronic lymphocytic leukemia.Blood advances · 2025Pooled it
- Prognostic significance of in patients with chronic lymphocytic leukemia: A meta-analysis.Annals of hematology · 2025Pooled it
- Minimal residual disease-guided ibrutinib and venetoclax in patients with chronic lymphocytic leukaemia and complex karyotype.British journal of haematology · 2026Article
- To Treat or Not to Treat: Navigating Early-Stage CLL in the Era of Targeted Therapy.European journal of haematology · 2026Review
- ZNF292 mutations impair RNA and protein biosynthesis defining an adverse prognostic subset in early-stage chronic lymphocytic leukemia.Biomarker research · 2026Article
- Aberrant expression of MERTK activates BCR via CD79a in CLL cells: alternative therapeutic strategy for relapsed/refractory CLL.Leukemia · 2026Article
- MYD88L265P mutation is a highly specific marker for the nonGCB/ABC DLBCL molecular subtype.Virchows Archiv : an international journal of pathology · 2026Article
- Comparative evaluation of two NGS-based assays for somatic hypermutation analysis of IGHV genes in chronic lymphocytic leukemia.Blood research · 2026Article
- Molecular and functional characterization of the B-cell receptor in chronic lymphocytic leukemia-like monoclonal B-cell lymphocytosis.Leukemia · 2026Article
- IGHV1 usage is associated with lymphadenopathy and aggressive disease in the TCL1 mouse model for chronic lymphocytic leukemia.Scientific reports · 2025Article
- ATM aberrations in chronic lymphocytic leukemia: del(11q) rather than ATM mutations is an adverse-prognostic biomarker.Leukemia · 2025Article
- Mutational heterogeneities in STAT3 and clonal hematopoiesis-related genes in acquired pure red cell aplasia.Annals of hematology · 2025Article
- Ibrutinib enhances the bias of T cell responses towards staphylococcal superantigens sustaining inflammation in chronic lymphocytic leukaemia.Frontiers in immunology · 2025Article
- The Danish Lymphoid Cancer Research (DALY-CARE) Data Resource: The Basis for Developing Data-Driven Hematology.Clinical epidemiology · 2025Article
- Article
- Recent Advances in the Molecular Biology of Chronic Lymphocytic Leukemia: How to Define Prognosis and Guide Treatment.Cancers · 2024Review
- MYC-rearranged mature B-cell lymphomas in children and young adults are molecularly Burkitt Lymphoma.Blood cancer journal · 2024Article
- Unveiling the dynamics and molecular landscape of a rare chronic lymphocytic leukemia subpopulation driving refractoriness: insights from single-cell RNA sequencing.Molecular oncology · 2024Article
- MicroRNA Profiling as a Predictive Indicator for Time to First Treatment in Chronic Lymphocytic Leukemia: Insights from the O-CLL1 Prospective Study.Non-coding RNA · 2024Article
- ERIC recommendations for TP53 mutation analysis in chronic lymphocytic leukemia-2024 update.Leukemia · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
61 authors at 20 institutions in 13 countries.
Larry Mansouri *Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Birna Thorvaldsdottir *Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-7372-9925
Lesley-Ann Sutton *Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Georgios KarakatsoulisCentre for Research and Technology Hellas, Institute of Applied Biosciences, Thessaloniki, Greece.
Manja MeggendorferMLL Munich Leukemia Laboratory, Munich, Germany.
Helen ParkerCancer Genomics, School for Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Ferran NadeuInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.ORCID http://orcid.org/0000-0003-2910-9440
Christian BrieghelDepartment of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-1816-8106
Stamatia LaidouCentre for Research and Technology Hellas, Institute of Applied Biosciences, Thessaloniki, Greece.ORCID http://orcid.org/0000-0002-4636-1579
Riccardo MoiaDivision of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.ORCID http://orcid.org/0000-0001-7393-1138
Davide RossiDivision of Hematology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Mark CatherwoodPatrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.
Jana KotaskovaDepartment of Internal Medicine-Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.ORCID http://orcid.org/0000-0003-1672-7346
Julio DelgadoInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Ana E Rodríguez-VicenteCancer Research Center (IBMCC) CSIC-University of Salamanca, Salamanca, Spain.ORCID http://orcid.org/0000-0001-6516-2172
Rocío BenitoCancer Research Center (IBMCC) CSIC-University of Salamanca, Salamanca, Spain.ORCID http://orcid.org/0000-0001-9781-4198
Gian Matteo RigolinHematology-Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
Silvia BonfiglioUniversità Vita Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy.
Lydia ScarfoUniversità Vita Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy.
Mattias MattssonDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Zadie DavisMolecular Pathology Department, University Hospitals Dorset, Bournemouth, UK.ORCID http://orcid.org/0000-0001-6959-4853
Ajay GogiaAll India Institute of Medical Sciences (AIIMS), New Delhi, India.
Lata RaniAll India Institute of Medical Sciences (AIIMS), New Delhi, India.
Panagiotis BaliakasDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0002-5634-7156
Hassan Foroughi-AslDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-6925-9040
Cecilia JylhäDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Aron SkaftasonDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Inmaculada RapadoHospital Universitario 12 Octubre, Madrid, Spain.
Fatima MirasHospital Universitario 12 Octubre, Madrid, Spain.
Joaquín Martinez-LopezHospital Universitario 12 Octubre, Madrid, Spain.
Javier de la SernaHospital Universitario 12 Octubre, Madrid, Spain.ORCID http://orcid.org/0000-0003-3904-1101
Jesús María Hernández RivasCancer Research Center (IBMCC) CSIC-University of Salamanca, Salamanca, Spain.
Patrick ThorntonHaematology Department, Beaumont Hospital, Dublin, Ireland.
María José LarráyozHematological Diseases Laboratory, CIMA LAB Diagnostics, University of Navarra, Pamplona, Spain.
María José CalasanzHematological Diseases Laboratory, CIMA LAB Diagnostics, University of Navarra, Pamplona, Spain.
Viktória FésüsHCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
Zoltán MátraiCentral Hospital of Southern Pest-National Institute of Hematology and Infectious Diseases, Budapest, Hungary.
Csaba BödörHCEMM-SE Molecular Oncohematology Research Group, Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.ORCID http://orcid.org/0000-0002-0729-692X
Karin E SmedbyClinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Blanca EspinetMolecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar and Translational Research on Hematological Neoplasms Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain.ORCID http://orcid.org/0000-0002-4294-8145
Anna PuiggrosMolecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar and Translational Research on Hematological Neoplasms Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
Ritu GuptaAll India Institute of Medical Sciences (AIIMS), New Delhi, India.ORCID http://orcid.org/0000-0001-5364-4086
Lars BullingerDepartment of Hematology, Oncology and Cancer Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Francesc BoschDepartment of Hematology, Hospital Universitari Vall d'Hebron (HUVH), Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Bárbara Tazón-VegaDepartment of Hematology, Hospital Universitari Vall d'Hebron (HUVH), Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Fanny Baran-MarszakService d'hématologie Biologique Hôpital Avicenne Assistance Publique des Hôpitaux de Paris, Bobigny, France.ORCID http://orcid.org/0000-0002-3723-2927
David OscierMolecular Pathology Department, University Hospitals Dorset, Bournemouth, UK.
Florence Nguyen-KhacSorbonne Université, Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, APHP, Paris, France.
Thorsten ZenzDepartment of Oncology and Haematology, University Hospital and University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0001-7890-9845
Maria Jose TerolDepartment of Hematology, INCLIVA Research Insitute, University of Valencia, Valencia, Spain.
Antonio CuneoHematology-Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
María Hernández-SánchezCancer Research Center (IBMCC) CSIC-University of Salamanca, Salamanca, Spain.ORCID http://orcid.org/0000-0001-9968-2782
Sarka PospisilovaDepartment of Internal Medicine-Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
Ken MillsPatrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.ORCID http://orcid.org/0000-0002-6362-4481
Gianluca GaidanoDivision of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.
Carsten U NiemannDepartment of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-9880-5242
Elias CampoInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.ORCID http://orcid.org/0000-0001-9850-9793
Jonathan C StreffordCancer Genomics, School for Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.ORCID http://orcid.org/0000-0002-0972-2881
Paolo GhiaUniversità Vita Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy.ORCID http://orcid.org/0000-0003-3750-7342
Kostas StamatopoulosDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-8529-640X
Richard RosenquistDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. richard.rosenquist@ki.se.ORCID http://orcid.org/0000-0002-0211-8788
Karolinska Institutet · SEUniversidad de Salamanca · ESAll India Institute of Medical Sciences · INSpanish National Cancer Research Centre · ESVita-Salute San Raffaele University · ITBournemouth University · GBCentral European Institute of Technology · CZCopenhagen University Hospital · DKHospital Clínic de Barcelona · ESHospital Del Mar · ESNavarre Institute of Health Research · ESQueen's University Belfast · GBSemmelweis University · HUUniversità degli Studi del Piemonte Orientale “Amedeo Avogadro” · ITUniversitat Autònoma de Barcelona · ESUniversity of Ferrara · ITUniversity of Southampton · GBUppsala University · SEBeaumont Hospital · IECentre for Research and Technology Hellas · GR
Funding
Cancer Research UK 23669Cancer Research UK 29370Cancer Research UK C24563/A15581Cancer Research UK C2750/A23669Cancer Research UK C34999/A18087Cancer Research UK C42023/A29370
Abstract
Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3-9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.
Indexed as
Leukemia, Lymphocytic, Chronic, B-CellHumansMutationMyeloid Differentiation Factor 88PhenotypePrognosisMyeloid Differentiation Factor 88
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LicenceCC BY
Read underepoch 390
Registered trials
NCT07499635ClinicalTrials.gov
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.