{"doi":"10.1002/ajh.27421","title":"Chronic lymphocytic leukemia patients with chromosome 6q deletion as the sole cytogenetic abnormality display a high frequency of <i>RPS15</i> mutations and have a poor prognosis","abstract":"Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, with survival times ranging from months to decades, reflecting a great biological diversity. Classical cytogenetical models allow to classify patients in different risk subgroups according to the presence of certain chromosomal aberrations, being the most common the 13q deletion (del(13q)), 17p deletion (del(17p)), 11q deletion (del(11q)), and trisomy 12 (+12).1 By contrast, other less frequent cytogenetic alterations, including 6q deletion (del(6q)), affects a lower but not insignificant percentage of patients (5%). Several studies have suggested an association of del(6q) with inferior outcomes, allocating these CLL cases in an intermediate-risk category,2, 3 although other studies have shown no difference in outcomes.4 The recurrence of del(6q) in other B-cell malignancies strongly suggests that this region contains unidentified tumor-suppressor gene(s). Nevertheless, CLL patients harboring del(6q) remain poorly characterized at the molecular level, partly due to the low incidence of cases, the lack of a FISH-based routinely assessment of del(6q), and the co-occurrence with other abnormalities that masks their clinical and biological significance. Here, we comprehensively characterize for the first time the genetic landscape of CLL patients with del(6q) identified by karyotyping, since we believe that a mutational screening could allow for refinement in predicting overall survival and time to first treatment, as well as provide novel insights into del(6q) CLL pathobiology. To this aim, patients' samples and clinical data were collected from four different institutions: Brigham and Women's Hospital (Boston, MA, USA), Massachusetts General Hospital (Boston, MA, USA), Hospital of Ferrara (Italy), and University Hospital of Salamanca (Spain), diagnosed according to the International Workshop on CLL criteria. The study was approved by the local ethical committees. Conventional cytogenetics were performed to assess the presence of del(6q) in a total of 39 samples, either peripheral bloods or bone marrows (Table S1). In addition, interphase FISH analysis was performed on all samples using the standard CLL FISH panel which include CEP12, D13S319/LSI13q34, ATM, and TP53. Mutational analysis was performed on genomic DNA from mononucleated cells by next-generation sequencing (NGS), and custom-designed libraries of exonic regions were used to assess the mutational status of 54 CLL-related candidate driver genes (Supplementary Methods). A control group was included in the study (n = 317) for survival, clinical, and molecular studies. Control group was representative of the disease in terms of clinical and biological characteristics and CLL-IPI scores, matched by gender and time of follow-up with the study group (Table S2). Statistical analyses were conducted in IBM SPSS v23.0 and R v4.0. Mann–Whitney U test was used for continuous variables, while chi-square and Fisher's exact tests were used to determine associations between categorical variables and patterns of mutual co-occurrence or exclusivity. Overall survival (OS) and time to first treatment (TTFT) were calculated from the date of cytogenetic analysis to the date of death, first treatment, or last follow-up (considering disease-unrelated deaths as competing events). Statistically significant variables related to OS and TTFT were estimated by the Kaplan–Meier method, using the log-rank test to compare the curves of each group. Results were considered statistically significant for values of p < .05. A total of thirty-eight patients with CLL had a del(6q) identified by karyotyping. Del(6q) was observed as the sole abnormality in 15 samples. In addition, all these sample demonstrated a normal CLL FISH panel. In the remaining 23, del(6q) was present either with other cytogenetic alterations, or as additional no-related clone (Table S1). The whole series of 38 patients with del(6q) showed more adverse risk markers","journal":"American Journal of Hematology","year":2024,"id":500315,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9635,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1349258,"name":"Teresa González","orcid":"0000-0002-0930-0021","position":1,"is_corresponding":false},{"id":88277,"name":"Miguel Quijada Álamo","orcid":null,"position":2,"is_corresponding":false},{"id":1298693,"name":"Gian Matteo Rigolin","orcid":"0000-0002-8370-5190","position":3,"is_corresponding":false},{"id":841811,"name":"Adrian M. Dubuc","orcid":"0000-0002-3447-6715","position":4,"is_corresponding":false},{"id":1349259,"name":"Ángela Villaverde Ramiro","orcid":"0000-0002-7337-7218","position":5,"is_corresponding":false},{"id":1349670,"name":"Alberto Rodríguez‐Sánchez","orcid":null,"position":6,"is_corresponding":false},{"id":1349260,"name":"Araceli Ortíz‐Rubio","orcid":"0000-0002-7353-835X","position":7,"is_corresponding":false},{"id":1349261,"name":"Julio Dávila","orcid":"0000-0002-5185-2073","position":8,"is_corresponding":false},{"id":1349671,"name":"Ma. Jesús Vidal","orcid":null,"position":9,"is_corresponding":false},{"id":1349262,"name":"Isabel González-Gascón-y-Marín","orcid":"0000-0001-6329-1704","position":10,"is_corresponding":false},{"id":233573,"name":"José‐Ángel Hernández‐Rivas","orcid":"0000-0003-4550-757X","position":11,"is_corresponding":false},{"id":530730,"name":"Rocí­o Benito","orcid":"0000-0001-9781-4198","position":12,"is_corresponding":false},{"id":1349263,"name":"Virginia O. Volpe","orcid":"0000-0002-9872-1919","position":13,"is_corresponding":false},{"id":233541,"name":"Matthew S. Davids","orcid":"0000-0003-4529-2003","position":14,"is_corresponding":false},{"id":258324,"name":"Jeremy S. Abramson","orcid":"0000-0001-8467-9257","position":15,"is_corresponding":false},{"id":786077,"name":"Antonio Cuneo","orcid":"0000-0003-2001-1308","position":16,"is_corresponding":false},{"id":3259,"name":"Paola dal Cin","orcid":"0000-0002-7426-5293","position":17,"is_corresponding":false},{"id":1349672,"name":"Ana‐Eugenia Rodríguez‐Vicente","orcid":null,"position":18,"is_corresponding":false},{"id":530735,"name":"Jesús María Hernández‐Rivas","orcid":"0000-0002-9661-9371","position":19,"is_corresponding":false},{"id":1349257,"name":"Claudia Pérez‐Carretero","orcid":"0000-0002-2089-2742","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-19T02:10:04.829419Z","pmid":"38949404","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}