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.
Authors
- Livio Trentin (ORCID: https://orcid.org/0000-0003-1222-6149)
- Jennifer Ann Woyach (ORCID: https://orcid.org/0000-0002-3403-9144)
- Fanny Baran‐Marszak (ORCID: https://orcid.org/0000-0002-3723-2927)
- Florence Nguyen‐Khac (ORCID: https://orcid.org/0000-0003-3107-6668)
- Annalisa Martines (ORCID: https://orcid.org/0000-0002-4701-8457)
- Federica Frezzato (ORCID: https://orcid.org/0000-0001-7093-2493)
- Laura Bonaldi (ORCID: https://orcid.org/0000-0001-7101-3093)
- Claudia Haferlach (ORCID: https://orcid.org/0000-0002-6333-5049)
- Francesca Romana Mauro (ORCID: https://orcid.org/0000-0003-2425-9474)
- Alessandro Cellini (ORCID: https://orcid.org/0000-0003-1094-9992)
- Antonio Cuneo
- Shuhua Yi (ORCID: https://orcid.org/0000-0002-6291-812X)
- Lydia Scarfò (ORCID: https://orcid.org/0000-0002-0844-0989)
- Gian Matteo Rigolin (ORCID: https://orcid.org/0000-0002-8370-5190)
- Panagiotis Baliakas (ORCID: https://orcid.org/0000-0002-5634-7156)
- Andrea Visentin (ORCID: https://orcid.org/0000-0003-0271-7200)
- Kerry Anne Rogers (ORCID: https://orcid.org/0000-0001-5748-7874)
- Michael Doubek (ORCID: https://orcid.org/0000-0002-1269-6282)
- Κώστας Σταματόπουλος (ORCID: https://orcid.org/0000-0001-8529-640X)
- Eugen Tausch
- Zadie Davis (ORCID: https://orcid.org/0000-0001-6959-4853)
- Anastasia Athanasiadou
- Francesc Bosch (ORCID: https://orcid.org/0000-0001-9241-2886)
- Olga Kalashnikova (ORCID: https://orcid.org/0000-0002-1856-1055)
- Stefania Bortoluzzi (ORCID: https://orcid.org/0000-0001-8240-3070)
- Blanca Espinet (ORCID: https://orcid.org/0000-0002-4294-8145)
- Silvia Orsi
- Moritz Fürstenau (ORCID: https://orcid.org/0000-0002-6593-0140)
- Thomas Chatzikonstantinou (ORCID: https://orcid.org/0000-0003-4105-1253)
- Panagiotis Panagiotidis (ORCID: https://orcid.org/0000-0002-2105-402X)
- Arnon Philip Kater (ORCID: https://orcid.org/0000-0003-3190-1891)
- María José Terol (ORCID: https://orcid.org/0000-0002-9467-932X)
- Alberto Valiente
- Anna Puiggros
- Karla Plevová (ORCID: https://orcid.org/0000-0002-6148-8877)
- Francesco Angotzi (ORCID: https://orcid.org/0000-0001-7835-2573)
- Valeria Ruocco
- Giulia Calabretto (ORCID: https://orcid.org/0000-0001-8646-2932)
- Paolo Ghia (ORCID: https://orcid.org/0000-0003-3750-7342)
- Enrico Gaffo (ORCID: https://orcid.org/0000-0001-6338-7677)
- Cecelia Miller (ORCID: https://orcid.org/0000-0001-6110-6069)
- Eleonora Roncaglia
- Pau Abrisqueta (ORCID: https://orcid.org/0000-0003-3028-7500)
- David Oscier (ORCID: https://orcid.org/0000-0001-8486-2051)
- Karl‐Anton Kreuzer
- Andrea Serafin
- Chenghua Cui
- Barbara Eichhorst
Institutions
- Uppsala University (SE)
- University of Padua (IT)
- Vita-Salute San Raffaele University (IT)
- University of Cologne (DE)
- Universität Ulm (DE)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- University of Ferrara (IT)
- Masaryk University (CZ)
- First Pavlov State Medical University of St. Petersburg (RU)
- Royal Bournemouth Hospital (GB)
- Science for Life Laboratory (SE)
- Sorbonne Université (FR)
- Munich Leukemia Laboratory (Germany) (DE)
- Hospital Clínico Universitario de Valencia (ES)
- Assistance Publique – Hôpitaux de Paris (FR)
- Complejo Hospitalario de Navarra (ES)
- Istituto Oncologico Veneto (IT)
- Pitié-Salpêtrière Hospital (FR)
- Arcispedale Sant'Anna (IT)
- Vall d'Hebron Hospital Universitari (ES)
- Hôpital Avicenne (FR)
- Hospital Del Mar (ES)
- IRCCS Ospedale San Raffaele (IT)
- Centre for Research and Technology Hellas (GR)
- Institute of Hematology & Blood Diseases Hospital (CN)
- G. Papanikolaou General Hospital (GR)
- Cancer Center Amsterdam (NL)
- Vall d'Hebron Institute of Oncology (ES)
- The Ohio State University (US)
- Athens State University (US)
- Sapienza University of Rome (IT)
- Universidad de Navarra (ES)
Publication Details
- Journal
- Leukemia
- Published
- 2025-09-19
- DOI
- https://doi.org/10.1038/s41375-025-02755-8
- Citations
- 1
- Primary Topic
- Chronic Lymphocytic Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 1.63
Funders
- Università degli Studi di Milano
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Università degli Studi di Padova
- Associazione Italiana per la Ricerca sul Cancro
- Hellenic Foundation for Research and Innovation