{"title":"慢性淋巴细胞白血病患者携带t的临床和转录组学特征(14;19):一项ERIC研究。","authors":"Andrea Visentin,Enrico Gaffo,Moritz Fürstenau,Kerry A Rogers,Baliakas Panagiotis,Chenghua Cui,Cecelia Miller,Claudia Haferlach,Karla Plevova,David Oscier,Zadie Davis,Florence Nguyen-Khac,Eleonora Roncaglia,Gian Matteo Rigolin,Anastasia Athanasiadou,Fanny Baran-Marszak,Alberto Valiente,Maria José Terol,Pau Abrisqueta,Blanca Espinet,Anna Puiggros,Annalisa Martines,Laura Bonaldi,Francesca Romana Mauro,Lydia Scarfò,Thomas Chatzikonstantinou,Eugen Tausch,Karl-Anton Kreuzer,Arnon Kater,Francesc Bosch,Michael Doubek,Panagiotis Panagiotidis,Olga Kalashnikova,Federica Frezzato,Giulia Calabretto,Valeria Ruocco,Silvia Orsi,Alessandro Cellini,Francesco Angotzi,Andrea Serafin,Shuhua Yi,Barbara Eichhorst,Jennifer A Woyach,Antonio Cuneo,Paolo Ghia,Kostas Stamatopoulos,Livio Trentin,Stefania Bortoluzzi","doi":"10.1038/s41375-025-02755-8","DOIUrl":null,"url":null,"abstract":"In chronic lymphocytic leukemia (CLL), the role of complex karyotype (CK) for prognostic stratification remains a topic of debate, and the impact of specific cytogenetic abnormalities is still unclear. This study aims to investigate the clinical and biological features of CLL with t(14;19)(q32;q13) (tCLL) involving the BCL3 gene. Patients with tCLL were younger and more commonly presented unmutated IGHV gene, subset #8 stereotypy, trisomy of chromosome 12, and complex karyotype than other patients without t(14;19) (oCLL). The presence of t(14;19) was associated with a shorter time to treatment and overall survival compared to oCLL. Gene expression analysis revealed a unique transcriptome profile in tCLL, characterized by the upregulation of BCL3 and the activation of B-cell receptor, PI3K-Akt. Conversely, apoptosis-related pathways were suppressed in tCLL. While the BTK gene was upregulated, the BCL2L11 gene, coding for the pro-apoptotic protein BIM, was downregulated. Notably, patients with tCLL were characterized by a trend (p = 0.058) for a longer time to the next treatment with BTK inhibitors (BTKi) compared to those treated with a venetoclax-based (Ven-based) regimen. We underscore the adverse outcomes of tCLL, its distinct molecular features and gene expression patterns. Therefore, our data suggest that identifying tCLL could help tailor therapeutic approaches.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"29 1","pages":""},"PeriodicalIF":13.4000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clinical and transcriptomic characterization of patients with chronic lymphocytic leukemia harboring t(14;19): an ERIC study.\",\"authors\":\"Andrea Visentin,Enrico Gaffo,Moritz Fürstenau,Kerry A Rogers,Baliakas Panagiotis,Chenghua Cui,Cecelia Miller,Claudia Haferlach,Karla Plevova,David Oscier,Zadie Davis,Florence Nguyen-Khac,Eleonora Roncaglia,Gian Matteo Rigolin,Anastasia Athanasiadou,Fanny Baran-Marszak,Alberto Valiente,Maria José Terol,Pau Abrisqueta,Blanca Espinet,Anna Puiggros,Annalisa Martines,Laura Bonaldi,Francesca Romana Mauro,Lydia Scarfò,Thomas Chatzikonstantinou,Eugen Tausch,Karl-Anton Kreuzer,Arnon Kater,Francesc Bosch,Michael Doubek,Panagiotis Panagiotidis,Olga Kalashnikova,Federica Frezzato,Giulia Calabretto,Valeria Ruocco,Silvia Orsi,Alessandro Cellini,Francesco Angotzi,Andrea Serafin,Shuhua Yi,Barbara Eichhorst,Jennifer A Woyach,Antonio Cuneo,Paolo Ghia,Kostas Stamatopoulos,Livio Trentin,Stefania Bortoluzzi\",\"doi\":\"10.1038/s41375-025-02755-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"In chronic lymphocytic leukemia (CLL), the role of complex karyotype (CK) for prognostic stratification remains a topic of debate, and the impact of specific cytogenetic abnormalities is still unclear. This study aims to investigate the clinical and biological features of CLL with t(14;19)(q32;q13) (tCLL) involving the BCL3 gene. Patients with tCLL were younger and more commonly presented unmutated IGHV gene, subset #8 stereotypy, trisomy of chromosome 12, and complex karyotype than other patients without t(14;19) (oCLL). The presence of t(14;19) was associated with a shorter time to treatment and overall survival compared to oCLL. Gene expression analysis revealed a unique transcriptome profile in tCLL, characterized by the upregulation of BCL3 and the activation of B-cell receptor, PI3K-Akt. Conversely, apoptosis-related pathways were suppressed in tCLL. While the BTK gene was upregulated, the BCL2L11 gene, coding for the pro-apoptotic protein BIM, was downregulated. Notably, patients with tCLL were characterized by a trend (p = 0.058) for a longer time to the next treatment with BTK inhibitors (BTKi) compared to those treated with a venetoclax-based (Ven-based) regimen. We underscore the adverse outcomes of tCLL, its distinct molecular features and gene expression patterns. Therefore, our data suggest that identifying tCLL could help tailor therapeutic approaches.\",\"PeriodicalId\":18109,\"journal\":{\"name\":\"Leukemia\",\"volume\":\"29 1\",\"pages\":\"\"},\"PeriodicalIF\":13.4000,\"publicationDate\":\"2025-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Leukemia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41375-025-02755-8\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Leukemia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41375-025-02755-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Clinical and transcriptomic characterization of patients with chronic lymphocytic leukemia harboring t(14;19): an ERIC study.
In chronic lymphocytic leukemia (CLL), the role of complex karyotype (CK) for prognostic stratification remains a topic of debate, and the impact of specific cytogenetic abnormalities is still unclear. This study aims to investigate the clinical and biological features of CLL with t(14;19)(q32;q13) (tCLL) involving the BCL3 gene. Patients with tCLL were younger and more commonly presented unmutated IGHV gene, subset #8 stereotypy, trisomy of chromosome 12, and complex karyotype than other patients without t(14;19) (oCLL). The presence of t(14;19) was associated with a shorter time to treatment and overall survival compared to oCLL. Gene expression analysis revealed a unique transcriptome profile in tCLL, characterized by the upregulation of BCL3 and the activation of B-cell receptor, PI3K-Akt. Conversely, apoptosis-related pathways were suppressed in tCLL. While the BTK gene was upregulated, the BCL2L11 gene, coding for the pro-apoptotic protein BIM, was downregulated. Notably, patients with tCLL were characterized by a trend (p = 0.058) for a longer time to the next treatment with BTK inhibitors (BTKi) compared to those treated with a venetoclax-based (Ven-based) regimen. We underscore the adverse outcomes of tCLL, its distinct molecular features and gene expression patterns. Therefore, our data suggest that identifying tCLL could help tailor therapeutic approaches.
期刊介绍:
Title: Leukemia
Journal Overview:
Publishes high-quality, peer-reviewed research
Covers all aspects of research and treatment of leukemia and allied diseases
Includes studies of normal hemopoiesis due to comparative relevance
Topics of Interest:
Oncogenes
Growth factors
Stem cells
Leukemia genomics
Cell cycle
Signal transduction
Molecular targets for therapy
And more
Content Types:
Original research articles
Reviews
Letters
Correspondence
Comments elaborating on significant advances and covering topical issues