{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:54:22Z","timestamp":1760147662190,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T00:00:00Z","timestamp":1676851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Chronic lymphocytic leukemia (CLL) is one of the most common B-cell malignancies in Western countries. IGHV mutational status is the most important prognostic factor for this disease. CLL is characterized by an extreme narrowing of the IGHV genes repertoire and the existence of subgroups of quasi-identical stereotyped antigenic receptors (SAR). Some of these subgroups have already been identified as independent prognostic factors for CLL. Here, we report the frequencies of TP53, NOTCH1, and SF3B1 gene mutations and chromosomal aberrations assessed by NGS and FISH in 152 CLL patients with the most common SAR in Russia. We noted these lesions to be much more common in patients with certain SAR than average in CLL. The profile of these aberrations differs between the subgroups of SAR, despite the similarity of their structure. For most of these subgroups mutations prevailed in a single gene, except for CLL#5 with all three genes affected by mutations. It should be noted that our data concerning the mutation frequency in some SAR groups differ from that obtained previously, which could be due to the population differences between patient cohorts. The research in this area should be important for better understanding the pathogenesis of CLL and therapy optimization.<\/jats:p>","DOI":"10.3390\/genes14020532","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T02:30:35Z","timestamp":1676946635000},"page":"532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Lesions in Russian CLL Patients with the Most Common Stereotyped Antigen Receptors"],"prefix":"10.3390","volume":"14","author":[{"given":"Bella V.","family":"Biderman","sequence":"first","affiliation":[{"name":"National Medical Research Center for Hematology, Novy Zykovski lane 4a, Moscow 125167, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina B.","family":"Likold","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Hematology, Novy Zykovski lane 4a, Moscow 125167, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nataliya A.","family":"Severina","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Hematology, Novy Zykovski lane 4a, Moscow 125167, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1613-652X","authenticated-orcid":false,"given":"Tatiana N.","family":"Obukhova","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Hematology, Novy Zykovski lane 4a, Moscow 125167, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9463-9187","authenticated-orcid":false,"given":"Andrey B.","family":"Sudarikov","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Hematology, Novy Zykovski lane 4a, Moscow 125167, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1172\/JCI3009","article-title":"Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors","volume":"102","author":"Fais","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1182\/blood.V94.6.1840","article-title":"Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia","volume":"94","author":"Damle","year":"1999","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1182\/blood.V94.6.1848","article-title":"Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia","volume":"94","author":"Hamblin","year":"1999","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1038\/s41375-022-01604-2","article-title":"ERIC, the European Research Initiative on CLL. Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: The 2022 update of the recommendations by ERIC, the European Research Initiative on CLL","volume":"36","author":"Agathangelidis","year":"2022","journal-title":"Leukemia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/978-1-4939-9151-8_7","article-title":"Stereotyped B Cell Receptor Immunoglobulins in B Cell Lymphomas","volume":"1956","author":"Agathangelidis","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1038\/leu.2017.125","article-title":"Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: Updated ERIC recommendations","volume":"31","author":"Rosenquist","year":"2017","journal-title":"Leukemia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4952","DOI":"10.1182\/blood-2002-11-3485","article-title":"Chronic lymphocytic leukemias utilizing the VH3-21 gene display highly restricted Vlambda 2-14 gene use and homologous CDR3s: Implicating recognition of a common antigen epitope","volume":"101","author":"Tobin","year":"2003","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1182\/blood-2004-01-0132","article-title":"Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia","volume":"104","author":"Tobin","year":"2004","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1182\/blood-2004-03-0818","article-title":"Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins","volume":"104","author":"Widhopf","year":"2004","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1084\/jem.20040544","article-title":"Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen inpromoting chronic lymphocytic leukemia","volume":"200","author":"Messmer","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3575","DOI":"10.1182\/blood-2005-04-1511","article-title":"Immunoglobulin light chain repertoire in chronic lymphocytic leukemia","volume":"106","author":"Stamatopoulos","year":"2005","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1182\/blood.2020007039","article-title":"Higher-order onnections between stereotyped subsets: Implications for improved patient classification in CLL","volume":"137","author":"Agathangelidis","year":"2021","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1111\/bjh.12893","article-title":"The frequency of TP53 gene defects differs between chronic lymphocytic leukaemia subgroups harbouring distinct antigen receptors","volume":"166","author":"Malcikova","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1038\/leu.2013.98","article-title":"Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia: The case of SF3B1 and subset #2","volume":"27","author":"Strefford","year":"2013","journal-title":"Leukemia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.4161\/epi.22901","article-title":"Distinct transcriptional control in major immunogenetic subsets of chronic lymphocytic leukemia exhibiting subset-biased global DNA methylation profiles","volume":"7","author":"Kanduri","year":"2012","journal-title":"Epigenetics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.3324\/haematol.2010.028639","article-title":"Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors","volume":"95","author":"Marincevic","year":"2010","journal-title":"Haematologica"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2119\/molmed.2013.00005","article-title":"Differential microRNA profiles and their functional implications in different immunogenetic subsets of chronic lymphocytic leukemia","volume":"19","author":"Papakonstantinou","year":"2013","journal-title":"Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.3109\/10428194.2015.1028051","article-title":"Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia","volume":"56","author":"Maura","year":"2015","journal-title":"Leuk. Lymphoma"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4902","DOI":"10.1182\/blood-2013-02-486209","article-title":"Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia","volume":"121","author":"Rossi","year":"2013","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"959","DOI":"10.3324\/haematol.2016.141812","article-title":"Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors","volume":"101","author":"Sutton","year":"2016","journal-title":"Haematologica"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1182\/blood-2020-140663","article-title":"Genetic lesions in Russian CLL patients with the most common stereotyped antigen receptors","volume":"136","author":"Biderman","year":"2020","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"360","DOI":"10.3324\/haematol.2018.195032","article-title":"Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia","volume":"104","author":"Baliakas","year":"2019","journal-title":"Haematologica"},{"key":"ref_23","unstructured":"Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., and Thiele, J. (2017). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, WHO. [4th ed.]."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e938","DOI":"10.1016\/j.clml.2021.07.005","article-title":"Repertoire of Rearranged Immunoglobulin Heavy Chain Genes in Russian Patients With B-Cell Lymphoproliferative Diseases","volume":"21","author":"Biderman","year":"2021","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_25","unstructured":"(1995, July 31). DNA Prep For Eukaryotic Cells. Available online: http:\/\/www.bio.net\/bionet\/mm\/methods-and-reagents\/1995-July\/031231.html."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0161-5890(92)90100-C","article-title":"Use of family specific leader region primers for PCR amplification of the human heavy chain variable region repertoire","volume":"29","author":"Campbell","year":"1992","journal-title":"Mol. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1038\/sj.leu.2403202","article-title":"Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936","volume":"17","author":"Langerak","year":"2003","journal-title":"Leukemia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"W503","DOI":"10.1093\/nar\/gkn316","article-title":"IMGT\/V-QUEST: The highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis","volume":"36","author":"Brochet","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3844","DOI":"10.1093\/bioinformatics\/btv456","article-title":"ARResT\/AssignSubsets: A novel application for robust subclassification of chronic lymphocytic leukemia based on B cell receptor IG stereotypy","volume":"31","author":"Bystry","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4247908","DOI":"10.1155\/2016\/4247908","article-title":"A Novel Assay for the Identification of NOTCH1 PEST Domain Mutations in Chronic Lymphocytic Leukemia","volume":"2016","author":"Campregher","year":"2016","journal-title":"Biomed. Res. Int."},{"key":"ref_31","first-page":"63","article-title":"Detection and Functional Analysis of TP53 Mutations in CLL","volume":"1881","author":"Pavlova","year":"2019","journal-title":"Nat. Chronic Lymphocytic Leuk. Methods Protoc. Methods Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez, J.A., Hern\u00e1ndez-S\u00e1nchez, M., Rodr\u00edguez-Vicente, A.E., Grossmann, V., Collado, R., Heras, C., Puiggros, A., Mart\u00edn, A.A., Puig, N., and Benito, R. (2015). A Low Frequency of Losses in 11q Chromosome Is Associated with Better Outcome and Lower Rate of Genomic Mutations in Patients with Chronic Lymphocytic Leukemia. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143073"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina Sequence Data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","article-title":"Fast and accurate long-read alignment with Burrows-Wheeler transform","volume":"26","author":"Li","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1093\/nar\/gkw227","article-title":"VarDict: A novel and versatile variant caller for next-generation sequencing in cancer research","volume":"44","author":"Lai","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_38","unstructured":"(2022, January 15). Seshat. Available online: http:\/\/vps338341.ovh.net\/."},{"key":"ref_39","unstructured":"(2022, January 15). COSMIC (Catalogue of Somatic Mutations in Cancer). Available online: https:\/\/cancer.sanger.ac.uk\/cosmic."},{"key":"ref_40","unstructured":"(2022, January 15). Franklin by Genoox. Available online: https:\/\/franklin.genoox.com\/."},{"key":"ref_41","unstructured":"McGowan-Jordan, J., Simons, A., and Schmid, M. (2016). ISCN: An International System for Human Cytogenomic Nomenclature, Karger."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"McGowan-Jordan, J., Hastings, R.J., and Moore, S. (2020). ISCN 2020: An International System for Human Cytogenomic Nomenclature, Karger.","DOI":"10.1159\/isbn.978-3-318-06867-2"},{"key":"ref_43","first-page":"130","article-title":"Detection of deletion 17p13\/tp53 in chronic lymphocytic leukemia by ARRAY-CGH method","volume":"67","author":"Obukhova","year":"2022","journal-title":"Hematol. Transfusiology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1182\/blood-2018-09-873083","article-title":"Cytogenetic complexity in chronic lymphocytic leukemia: Definitions, associations, and clinical impact","volume":"133","author":"Baliakas","year":"2019","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1002\/ajh.24282","article-title":"Chronic lymphocytic leukemia (CLL)\u2014Then and now","volume":"91","author":"Rai","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1038\/leu.2013.218","article-title":"Prognostic impact and landscape of NOTCH1 mutations in chronic lymphocytic leukemia (CLL): A study on 852 patients","volume":"27","author":"Weissmann","year":"2013","journal-title":"Leukemia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1182\/blood-2011-09-379966","article-title":"Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia","volume":"119","author":"Rossi","year":"2012","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/leu.2013.263","article-title":"SF3B1 mutations correlated to cytogenetics andmutations in NOTCH1, FBXW7, MYD88,XPO1 and TP53 in 1160 untreated CLLpatients","volume":"28","author":"Jeromin","year":"2014","journal-title":"Leukemia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.3109\/10428194.2014.898760","article-title":"NOTCH1, SF3B1, BIRC3 and TP53 mutations in patients with chronic lymphocytic leukemia undergoing first-line treatment: Correlation with biological parameters and response to treatment","volume":"55","author":"Chiaretti","year":"2014","journal-title":"Leuk. Lymph."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1002\/ajh.25956","article-title":"The complex karyotype and chronic lymphocytic leukemia: Prognostic value and diagnostic recommendations","volume":"95","author":"Jondreville","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.cell.2013.01.019","article-title":"Evolution and impact of subclonal mutations in chronic lymphocytic leukemia","volume":"152","author":"Landau","year":"2013","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"604","DOI":"10.3324\/haematol.2020.265777","article-title":"Clonal evolution in chronic lymphocytic leukemia is scant in relapsed but accelerated in refractory cases after chemo(immune) therapy","volume":"107","author":"Zapatka","year":"2022","journal-title":"Haematologica"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e158","DOI":"10.3324\/haematol.2017.182634","article-title":"No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy","volume":"103","author":"Baliakas","year":"2018","journal-title":"Haematologica"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"771454","DOI":"10.3389\/fonc.2021.771454","article-title":"Distinctive Signaling Profiles with Distinct biological and Clinical Implications in Aggressive CLL Subsets With Stereotyped B-Cell Receptor Immunoglobulin","volume":"11","author":"Gerousi","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1016\/S2352-3026(14)00005-2","article-title":"Clinical Effect of Stereotyped B-Cell Receptor Immunoglobulins in Chronic Lymphocytic Leukaemia: A Retrospective Multicentre Study","volume":"1","author":"Baliakas","year":"2014","journal-title":"Lancet Haematol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/ajh.23342","article-title":"B-cell receptor configuration and adverse cytogenetics are associated with autoimmune hemolytic anemia in chronic lymphocytic leukemia","volume":"88","author":"Maura","year":"2013","journal-title":"Am. J. Hematol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5292","DOI":"10.1158\/1078-0432.CCR-16-3100","article-title":"Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes","volume":"23","author":"Xochelli","year":"2017","journal-title":"Clin. Cancer. Res."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/2\/532\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:37:25Z","timestamp":1760121445000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/2\/532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,20]]},"references-count":57,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["genes14020532"],"URL":"https:\/\/doi.org\/10.3390\/genes14020532","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2023,2,20]]}}}