Clinical and transcriptomic characterization of patients with chronic lymphocytic leukemia harboring t(14;19): an ERIC study
Year: 2025
Type: article
Study design: Observational Study
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.
Source: Leukemia
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 P 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
Institutions: University of Padua, University of Cologne, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Uppsala University, Science for Life Laboratory, Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Hematology & Blood Diseases Hospital, State Key Laboratory of Experimental Hematology, Munich Leukemia Laboratory (Germany), Masaryk University, University Hospital Brno, Royal Bournemouth Hospital, Pitié-Salpêtrière Hospital, University of Ferrara, Arcispedale Sant'Anna, G. Papanikolaou General Hospital, Assistance Publique – Hôpitaux de Paris, Laboratoire d'hématologie, Hospital Clínico Universitario de Valencia, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Hospital Del Mar, Hospital del Mar Research Institute, Istituto Oncologico Veneto, Sapienza University of Rome, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Centre for Research and Technology Hellas, Universität Ulm, Cancer Center Amsterdam, National and Kapodistrian University of Athens, First Pavlov State Medical University of St. Petersburg
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,190
OpenAlex ID: W4414347945