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Journal articles on the topic 'BCR intraclonal analysis'

Author: Grafiati

Published: 25 May 2024

Last updated: 31 July 2025

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1

Ng, Anita, Andrew Shih, Martina Cardillo, et al. "Investigation into Intraclonal Heterogeneity of CXCR4 DimCD5 Bright Chronic Lymphocytic Leukemia Cells Identifies Distinct Activation Signatures." Blood 142, Supplement 1 (2023): 3259. http://dx.doi.org/10.1182/blood-2023-187957.

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Chronic Lymphocytic Leukemia (CLL) is a heterogeneous disease associated with diverse clinical and molecular profiles, suggesting long-term clonal evolution driven by genetic diversification from a small, often undetected, subset of leukemic cells endowed with superior growth capacities. More importantly, this diversification process enhances the opportunity of CLL subclones to survive selective pressure, such as BTK or PLCG2 mutations that can abolish the effect of BTK inhibitors. While this evolutionary process is inevitable in leukemic cells, therapeutic intervention targeting the cells tha

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2

Julien, Sylvie, Mirjana Radosavljevic, Nathalie Labouret, et al. "AIDS Primary Central Nervous System Lymphoma: Molecular Analysis of the Expressed VH Genes and Possible Implications for Lymphomagenesis." Journal of Immunology 162, no. 3 (1999): 1551–58. http://dx.doi.org/10.4049/jimmunol.162.3.1551.

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Abstract AIDS-associated primary central nervous system lymphomas are late events that have an extremely poor prognosis. Despite different hypotheses, the brain localization of these B cell lymphomas remains an enigma. To better define the cell origin of the lymphomas and the possible role of the B cell receptor (BCR) in the brain localization and/or in the oncogenic transformation, we analyzed the V region genes of the Ig heavy chain expressed by lymphoma cells in five randomly selected patients. After amplifying the rearranged VHDJH DNA by PCR, cloning, and sequencing of the amplified produc

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3

van Bergen, Cornelis A. M., Marvyn T. Koning, Edwin Quinten, et al. "High-Throughput BCR Sequencing and Single-Cell Transcriptomics Reveal Distinct Transcriptional Profiles Associated with Subclonal Evolution of Follicular Lymphoma." Blood 134, Supplement_1 (2019): 298. http://dx.doi.org/10.1182/blood-2019-130508.

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Objectives: Follicular lymphoma (FL) typically originates from premalignant mature B cells that carry the founder t(14;18) BCL2 translocation. Mutations in epigenetic modifiers and acquisition of N-glycosylation sites in CDR regions of the B-cell receptor (BCR) are recurrent secondary events in FL pathogenesis. Despite these oncogenic drivers, FL can remain indolent and clinically stable for years. The molecular events driving subclonal evolution into symptomatic progression and eventual transformation to aggressive lymphoma are insufficiently understood. FL cells are frozen in their B-cell de

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4

Zaragoza-Infante, Laura, Andreas Agathangelidis, Valentin Junet, et al. "Distinct Modes of Ongoing Antigen Interactions Shape Intraclonal Dynamics in Splenic Marginal Zone Lymphoma." Blood 138, Supplement 1 (2021): 1330. http://dx.doi.org/10.1182/blood-2021-148722.

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Abstract Almost one-third of all splenic marginal zone lymphoma (SMZL) cases express B cell receptor immunoglobulin (BcR IG) encoded by the IGHV1-2*04 gene. Such cases display a distinctive profile of genomic aberrations (e.g. higher incidence of NOTCH2 and KLF2 mutations) and a more aggressive clinical course compared to SMZL cases utilizing other IGHV genes. Such skewing of the BcR IG gene repertoire implicates antigen selection in SMZL ontogeny. Although the supportive evidence is compelling, it mostly derives from low-throughput approaches, which are inherently limited in their capacity to

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5

Yan, Xiao J., Wentian Li, Sophia Yancopoulos, et al. "Gene Expression Profiles Document That Recently- and Previously-Divided CLL Fractions Represent a Continuum but Suggest Differing Modes of Activation for These Fractions in U-CLL and M-CLL." Blood 120, no. 21 (2012): 317. http://dx.doi.org/10.1182/blood.v120.21.317.317.

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Abstract Abstract 317 By using reciprocal densities of surface membrane CXCR4 and CD5, chronic lymphocytic leukemia (CLL) B cells can be divided into 3 fractions indicating time since last division (proliferative, intermediate, and resting). It has been suggested that cells in these fractions represent a continuum from resting to intermediate to proliferative. In this study, we made intraclonal gene expression profile (GEP) comparisons of these fractions from 17 CLL patients to try to confirm this notion and interclonal comparisons between U-CLL and M-CLL patients to determine if pathways invo

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6

Iatrou, Anastasia, Marco Patrone, Ioannis Sarrigeorgiou, et al. "Structural and Functional Analysis of the Clonotypic B Cell Receptor Immunoglobulin in Splenic Marginal Zone Lymphoma: Ontogenetic and Therapeutic Implications." Blood 144, Supplement 1 (2024): 975. https://doi.org/10.1182/blood-2024-206746.

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Immunogenetic evidence implicates the B cell receptor immunoglobulin (BcR IG) in the natural history of splenic marginal zone lymphoma (SMZL). Indeed, SMZL carries distinct features of somatic hypermutation (SHM) amongst cases utilizing particular IGHV genes in their BcR IG. Moreover, the BcR IG gene repertoire in SMZL is restricted, whereby ~30% of cases utilize the IGHV1-2*04 gene and allele, notable for carrying a tryptophan (W) residue at position VH FR3-75 instead of the arginine (R) residue that is encoded by all remaining IGHV1-2 gene alleles and almost all other human IGHV genes and al

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7

Sutton, Lesley-Ann, Efterpi Kostareli, Anastasia Hadzidimitriou, et al. "Extensive Intraclonal Diversification in a Subgroup of Chronic Lymphocytic Leukemia Patients with Stereotyped IGHV4-34/IGKV2-30 B cell Receptors: Implications for Ongoing Interactions with Antigen." Blood 114, no. 22 (2009): 2337. http://dx.doi.org/10.1182/blood.v114.22.2337.2337.

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Abstract Abstract 2337 Poster Board II-314 Several studies indicate that the development of chronic lymphocytic leukemia (CLL) may be influenced by antigen (Ag) recognition through the clonotypic B cell receptors (BCRs). However, it is still unclear whether Ag involvement is restricted to the malignant transformation phase or whether the putative Ag(s) may continuously trigger the CLL clone. Valuable insight into these issues may be gleaned from the study of intraclonal diversification (ID) within the immunoglobulin (IG) genes through ongoing somatic hypermutation (SHM). Definitive data regard

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8

Packham, Graham, Serge Krysov, Vania Coelho, Peter Johnson, and Freda K. Stevenson. "A “Universal” Lectin-Mediated Interaction Drives B-Cell Receptor Signaling In Primary Follicular Lymphoma Cells." Blood 122, no. 21 (2013): 4291. http://dx.doi.org/10.1182/blood.v122.21.4291.4291.

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Abstract B-cell receptor (BCR) signaling has been identified as a critical driver of B-cell malignancies and as a target for therapeutic attack. Clinical responses to novel inhibitors of BCR-associated kinases have been relatively modest in follicular lymphoma (FL) and a more detailed knowledge of BCR function in these cells is required. Surface Ig (sIg) is unusual in FL since variable regions contain N-linked glycosylation sites which are introduced by somatic mutation. These are rarely found in normal B cells, indicating strong positive selective pressure in malignant cells. Remarkably, adde

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Sutton, Lesley-Ann, Efterpi Kostareli, Evangelia Stalika, et al. "Active Crosstalk with the Microenvironment Leading to Clonal Evolution in Chronic Lymphocytic Leukemia with Stereotyped IGHV4–34/IGKV2–30 Antigen Receptors." Blood 120, no. 21 (2012): 2878. http://dx.doi.org/10.1182/blood.v120.21.2878.2878.

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Abstract Abstract 2878 We recently demonstrated that intraclonal diversification (ID) in the immunoglobulin (IG) genes of patients with chronic lymphocytic leukemia (CLL) was limited, with the outstanding exception of subset #4 cases (IGHV4–34/IGKV2–30). Subset #4 cases express IgG-switched antigen receptors carrying long VH CDR3s enriched in positively charged amino acid residues (especially arginine), with acidic residues introduced by somatic hypermutation (SHM) in critical positions of both the heavy and light chain variable domains. This group of patients, characterized clinically by an e

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10

Linley, Adam J., Beatriz Valle-Argos, Andrew J. Steele, Freda K. Stevenson, Francesco Forconi, and Graham Packham. "Increased Reactive Oxygen Species and the B-Cell Receptor in Chronic Lymphocytic Leukemia Signaling." Blood 124, no. 21 (2014): 3291. http://dx.doi.org/10.1182/blood.v124.21.3291.3291.

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Abstract Reactive oxygen species (ROS) play important roles in regulating cell signaling, replication and survival. Chronic lymphocytic leukemia (CLL) cells generally contain high levels of mitochondrial-derived ROS compared to normal B cells. However, there is considerable variation in ROS levels between individual samples. Previous studies have demonstrated that chemotherapy may exert an important influence on ROS levels since prior therapy was linked to increased ROS, potentially via accumulation of mitochondrial DNA damage. However, variability in ROS levels is also apparent between sample

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11

Baaklini, Sabrina, Alexandre Sarrabay, Camille Barthelemy, et al. "A Single Cell Atlas of Diffuse Large B Cell Lymphomas Reveals Distinct Cellular States Predictive of Outcomes." Blood 142, Supplement 1 (2023): 848. http://dx.doi.org/10.1182/blood-2023-173929.

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Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive B-cell lymphoma with high clinical and biological heterogeneity. Despite current effective immunochemotherapy, up to 40% of patients do not respond or develop refractory disease. DLBCL is characterized by two major cell-of-origin (COO) subtypes, germinal center B cell-like (GCB) and activated B cell-like (ABC), with recent research uncovering additional molecular subgroups based on genomic alterations or tumor microenvironment (TME) features. However, current classifiers use bulk or deconvolution profiling which blurs intra-tu

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12

Gemenetzi, Katerina, Andreas Agathangelidis, Lesley-Ann Sutton, et al. "Remarkable Functional Constraints on the Antigen Receptors of CLL Stereotyped Subset #2: High-Throughput Immunogenetic Evidence." Blood 132, Supplement 1 (2018): 1839. http://dx.doi.org/10.1182/blood-2018-99-119125.

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Abstract Subset #2 is the largest subset carrying stereotyped B cell receptor immunoglobulin (BcR IG) in chronic lymphocytic leukemia (CLL). This particular BcR IG is composed of heavy (HC) and light (LC) chains encoded by the IGHV3-21 and the lambda IGLV3-21 gene, respectively. The clonotypic IGHV3-21 genes display a variable load of somatic hypermutation (SHM), being mostly classified as mutated (M-CLL) but also including unmutated (U-CLL) cases. Subset #2 cases, independently of the SHM status, have a particularly dismal clinical outcome similar to that of patients with TP53 aberrations, al

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13

Ptacek, Jason, Erik Evensen, Greg Friedland, et al. "Single Cell Network Profiling (SCNP) Identifies Altered Signaling Between Patient Risk Groups in B-Cell Chronic Lymphocytic Leukemia (B-CLL)." Blood 120, no. 21 (2012): 2876. http://dx.doi.org/10.1182/blood.v120.21.2876.2876.

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Abstract Abstract 2876 Background: B-CLL follows a variable clinical course, with a subset of patients progressing quickly. The reasons for this outcome disparity are not fully understood; however, evidence suggests that B-cell receptor (BCR) signaling is a driving event in disease onset and progression. B-CLL cells also receive survival signals through additional receptors. SCNP is a multiparametric flow cytometry-based assay that measures, quantitatively at the single cell level, changes in intracellular signaling proteins in response to extracellular modulators. This provides a functional m

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14

Vardi, Anna, Andreas Agathangelidis, Evangelia Stalika, et al. "T Cell Receptor Gene Repertoire Restriction in Chronic Lymphocytic Leukemia with Stereotyped IGHV4–34/IGKV2–30 Antigen Receptors." Blood 120, no. 21 (2012): 3908. http://dx.doi.org/10.1182/blood.v120.21.3908.3908.

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Abstract Abstract 3908 Chronic lymphocytic leukemia (CLL) exhibits a remarkably skewed immunoglobulin (IG) gene repertoire mainly evident in the existence of subsets of patients with quasi-identical IGs in their B cell receptors (BcRs), collectively accounting for one-third of CLL patients. BcR stereotypy is strongly suggestive of clonal selection by a restricted set of antigens. However, it is not yet clear at which phase of clonal evolution these antigens act, or whether the stimulation is persistent. Furthermore, the possible role of antigens in the selection and activation of cognate T lym

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15

Lanham, Stuart, Luis Del Rio Fernandez, Stefano de Pretis, et al. "Single-Cell Transcriptional Characteristics of the Unresponsive Cluster Surviving Anergy in IGHV1-69 CLL." Blood 144, Supplement 1 (2024): 1847. https://doi.org/10.1182/blood-2024-210464.

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Both chronic lymphocytic leukemias with unmutated (U-CLL) and mutated IGHV genes (M-CLL) are characterized by a variable state of anergy, defined by (auto)antigen-induced downmodulation of levels and function of the tumor IgM on the CLL cell surface (sIgM). The degree of anergy informs CLL progression and response to BTK inhibitors (BTKi), whereby patients with high sIgM have a more rapid progression and shorter duration of response to BTKi. Anergy appears particularly obvious in U-CLL selecting IGHV1-69(51p1) allele, which is infrequently used by normal B cells and represents ~30% of U-CLL. I

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16

Mazzarello, Andrea Nicola, Mark Fitch, Anita Ng, et al. "Analyses of the Kinetics and Phenotype of Multiple Intraclonal CXCR4/CD5 B Cell Subsets Suggest Differences in Life Cycle Transitioning in CLL." Blood 138, Supplement 1 (2021): 2622. http://dx.doi.org/10.1182/blood-2021-154224.

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Abstract Chronic lymphocytic leukemia (CLL) is a heterogeneous disease so that defining the dynamic features of the clone and its intraclonal subpopulations are essential to understand disease pathogenesis and to develop novel, effective therapies. For instance, because cell division is linked with new mutations, the ability to preferentially select cells that recently divided allows studying the subpopulation(s) most likely responsible for disease progression and resistance to therapies. The intraclonal kinetics of CLL B cells have been studied in clonal subgroups defined by reciprocal surfac

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17

Odabashian, Mariette, Emanuela Carlotti, Shamzah Araf, et al. "Immunoglobulin Variable Region Gene Sequences Reveal N-Glycosylation Motifs As an Early and Stable Event in Follicular Lymphoma Pathology." Blood 132, Supplement 1 (2018): 4101. http://dx.doi.org/10.1182/blood-2018-99-112397.

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Abstract Introduction: Follicular lymphoma (FL) cells retain expression of a functional B cell receptor (BCR) despite the loss of one Ig allele due to the hallmark t14:18 translocation and ongoing somatic hypermutation (SHM) of the variable genes (V genes) which increases the likelihood of crippling mutations. SHM introduces N-glycosylation (N-gly) motifs within the V genes, a feature exclusively restricted to germinal centre (GC)-derived lymphomas. Oligosaccharides of the high mannose type are added to motifs and interact with calcium-dependent lectins associated with cells of the microenviro

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18

Roulland, Sandrine, Julie Agopian, Mélanie Briand, et al. "Long-Term Clonal Evolution of Circulating Follicular Lymphoma-Like B Cells in Healthy Individuals: An Early Pathway to Lymphomagenesis." Blood 110, no. 11 (2007): 185. http://dx.doi.org/10.1182/blood.v110.11.185.185.

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Abstract Follicular lymphoma (FL), one of the most common B cell non-Hodgkin’s lymphoma, is a germinal centre (GC)-derived malignancy, for which acquisition of the oncogenic t(14;18) translocation in the bone marrow constitute the genetic hallmark and early initiating event of FL pathogenesis. As t(14;18) is also present at low frequency in peripheral blood from healthy individuals (HI), it has been assumed that in HI, t(14;18) is carried by circulating quiescent naïve B-cells with restrained oncogenic potential. In sharp contrast, we recently demonstrated that in HI, t(14;18) is mainly carri

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Lanasa, Mark C., Sallie D. Allgood, Susan L. Slager, et al. "Family-Associated Monoclonal B Lymphocytosis Is Commonly Oligoclonal and Expresses Markers Associated with Adverse Risk in CLL." Blood 112, no. 11 (2008): 3144. http://dx.doi.org/10.1182/blood.v112.11.3144.3144.

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Abstract Background and Significance : Chronic lymphocytic leukemia (CLL) is the most heritable hematologic malignancy; however, no common CLL predisposition genes are known. Monoclonal B lymphocytosis (MBL) is a hematologic syndrome characterized by small accumulations of B lymphocytes in the peripheral blood. MBL has a CLL-like immunophenotype, may progress to overt CLL, and is over represented in CLL families. Therefore, MBL observed in the context of familial CLL may be a marker of inherited risk for development of CLL. Detailed characterization of family-associated MBL may also provide me

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Roulland, Sandrine, Nathalie Jouve, Agnes Bru, and Marie-Helene Delfau-Larue. "Somatic Mutation and Isotype Switch Events Outside Igv Gene Loci Provide New Evidence for a Role of Antigenic Challenge in Mantle Cell Lymphoma Etiology." Blood 126, no. 23 (2015): 2647. http://dx.doi.org/10.1182/blood.v126.23.2647.2647.

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Abstract Mantle cell lymphoma (MCL) represents 5-10% of B-cell lymphomas and generally exhibits an aggressive clinical behavior. t(11;14) translocation, the genetic hallmark and early initiating event of MCL pathogenesis, lead to the constitutive CCND1 expression and consequently to cell-cycle deregulation. However, t(11;14) is also present in the blood from rare healthy individuals indicating that alone the t(11;14) is not sufficientfor malignant transformation. It has long been assumed in MCL that t(11;14)+ cells were actually carried by circulating naive and antigen-inexperienced B-cells. Y

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Camus, Vincent, Mathieu Viennot, Victor Bobée, et al. "Clonal Dominance in Follicular Lymphoma: A Predictor of Poor Prognosis and Histological Transformation." Blood 144, Supplement 1 (2024): 4353. https://doi.org/10.1182/blood-2024-200543.

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Introduction Follicular lymphoma (FL) exhibits a highly variable course, sometimes resulting in histological transformation (HT) to higher-grade lymphoma, complicating clinical management and the prediction of individual outcomes. Each patient's tumor expresses a unique cell surface immunoglobulin (Ig) that may recognize antigens and/or transduce signals. Methods We performed high-throughput RNA sequencing (5' RACE) to simultaneously target the B- and T-cell Ig repertoires (BCR and TCR) in order to assess clonal dominance from bulk RNA samples of diagnostic FFPE biopsies. The data were correla

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22

Chen, Zhenghao, Gaspard Cretenet, Beatriz Valle-Argos, et al. "Effects of Ibrutinib on Metabolic Alterations and Micro-Environmental Signalling in Chronic Lymphocytic Leukaemia." Blood 136, Supplement 1 (2020): 36–37. http://dx.doi.org/10.1182/blood-2020-142839.

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Introduction. Altered metabolism is one of the hallmarks of cancer. CLL cells circulate between peripheral blood (PB) and lymph nodes (LN) which necessitates high metabolic plasticity. In LN, CLL cells receive proliferative and pro-survival signals from surrounding cells, and become metabolically activated. However, detailed insight into the altered metabolism of LN CLL and how this may be related to therapeutic responses is lacking. As it is technically difficult to obtain direct insight into CLL LN metabolism, we have applied a two-tiered strategy. By using PB samples taken from patients bef

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Damle, Rajendra N., Sonal Temburni, Cristina Sison, et al. "Reciprocal Densities of CXCR4 and CD5 Define Subfractions of Chronic Lymphocytic Leukemia Clones Differing in Phenotype and Response to Environmental Stimuli: Towards a Better Definition of Targetable Components of Leukemic Clones." Blood 124, no. 21 (2014): 3322. http://dx.doi.org/10.1182/blood.v124.21.3322.3322.

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Abstract Although chronic lymphocytic leukemia (CLL) is an accumulative disorder of CD5+ B cells, a proliferative fraction exists and the extent of this proliferation correlates with clinical course. We previously demonstrated heterogeneous in vivo labeling kinetics of cells in 3 clonal fractions sorted based on reciprocal densities of chemokine (C-X-C motif) receptor 4 (CXCR4) and CD5 from CLL cases recruited on an in vivo labeling study. In that study, the CXCR4dimCD5br fraction contained more 2H-labeled DNA and hence recently divided cells (proliferative fraction) than the CXCR4brCD5dim(res

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24

Macana, Yesid Alejandro Mariño, and Miguel Alonso Rodríguez Melo. "El punto de marchitez permanente (PMP) en melina (Gmelina arborea L. Roxb) para la Costa Caribe colombiana ¿una característica para la selección de clones?" Corpoica Ciencia y Tecnología Agropecuaria 11, no. 2 (2010): 116. http://dx.doi.org/10.21930/rcta.vol11_num2_art:201.

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<p>Gmelina arborea (melina), especie forestal introducida en Colombia, se planta en áreas de la costa norte de Colombia caracterizado por presentar relativamente largas estaciones secas con baja disponibilidad de agua edáfica, principal limitante de su productividad. Con el fin de asignar los mejores materiales de siembra a ofertas ecofisiológicas específicas, se ha avanzado en su mejoramiento genético, confirmando si sus respuestas fisiológicas al estrés hídrico sirven como parámetro de selección de clones tolerantes a la baja disponibilidad de agua. Este estudio, desarrollado bajo cond

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25

Jeusset, Lucile, Nika Abdollahi, Thibaud Verny, et al. "ViCloD, an interactive web tool for visualizing B cell repertoires and analyzing intraclonal diversities: application to human B-cell tumors." NAR Genomics and Bioinformatics 5, no. 2 (2023). http://dx.doi.org/10.1093/nargab/lqad064.

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Abstract High throughput sequencing of adaptive immune receptor repertoire (AIRR-seq) has provided numerous human immunoglobulin (IG) sequences allowing specific B cell receptor (BCR) studies such as the antigen-driven evolution of antibodies (soluble forms of the membrane-bound IG part of the BCR). AIRR-seq data allows researchers to examine intraclonal differences caused primarily by somatic hypermutations in IG genes and affinity maturation. Exploring this essential adaptive immunity process could help elucidate the generation of antibodies with high affinity or broadly neutralizing activit

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Gemenetzi, Katerina, Fotis Psomopoulos, Alejandra Carriles, et al. "HIGHER ORDER IMMUNOGLOBULIN REPERTOIRE RESTRICTIONS IN CLL: THE ILLUSTRATIVE CASE OF STEREOTYPED SUBSETS #2 AND #169." Blood, October 9, 2020. http://dx.doi.org/10.1182/blood.2020005216.

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Chronic lymphocytic leukemia (CLL) major stereotyped subset #2 (IGHV3-21/IGLV3-21, ~2.5% of all CLL) is an aggressive disease variant, irrespective of the somatic hypermutation (SHM) status of the clonotypic IGHV gene. Minor stereotyped subset #169 (IGHV3-48/IGLV3-21, ~0.2% of all CLL) is related to subset #2 as it displays a highly similar variable antigen-binding site. We further explored this relationship through next-generation sequencing and crystallographic analysis of the clonotypic B cell receptor immunoglobulin (BcR IG). Branching evolution of the predominant clonotype through intracl

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Bagnara, Davide, Catherine Tang, Jennifer R. Brown, et al. "Post-Transformation IGHV-IGHD-IGHJ Mutations in Chronic Lymphocytic Leukemia B Cells: Implications for Mutational Mechanisms and Impact on Clinical Course." Frontiers in Oncology 11 (May 25, 2021). http://dx.doi.org/10.3389/fonc.2021.640731.

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Analyses of IGHV gene mutations in chronic lymphocytic leukemia (CLL) have had a major impact on the prognostication and treatment of this disease. A hallmark of IGHV-mutation status is that it very rarely changes clonally over time. Nevertheless, targeted and deep DNA sequencing of IGHV-IGHD-IGHJ regions has revealed intraclonal heterogeneity. We used a DNA sequencing approach that achieves considerable depth and minimizes artefacts and amplification bias to identify IGHV-IGHD-IGHJ subclones in patients with prolonged temporal follow-up. Our findings extend previous studies, revealing intracl

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Bagnara, Davide, Tang Catherine, R. Brown Jennifer, et al. "Post-Transformation IGHV-IGHD-IGHJ Mutations in Chronic Lymphocytic Leukemia B Cells: Implications for Mutational Mechanisms and Impact on Clinical Course." July 23, 2021. https://doi.org/10.3389/fonc.2021.640731.

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Analyses of IGHV gene mutations in chronic lymphocytic leukemia (CLL) have had a major impact on the prognostication and treatment of this disease. A hallmark of IGHV-mutation status is that it very rarely changes clonally over time. Nevertheless, targeted and deep DNA sequencing of IGHV-IGHD-IGHJ regions has revealed intraclonal heterogeneity. We used a DNA sequencing approach that achieves considerable depth and minimizes artefacts and amplification bias to identify IGHV-IGHD-IGHJ subclones in patients with prolonged temporal follow-up. Our findings extend previous studies, revealing intracl

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