Roncaglia Eleonora, Gaffo Enrico, Calabretto Giulia, Fürstenau Moritz, Rogers Kerry A, Baliakas Panagiotis, Cui Chenghua, Miller Cecelia, Haferlach Claudia, Plevova Karla, Oscier David, Davis Zadie, Nguyen-Khac Florence, Rigolin Gian Matteo, Athanasiadou Anastasia, Baran-Marszak Fanny, Valiente Alberto, Terol Maria José, Abrisqueta Pau, Espinet Blanca, Puiggros Anna, Martines Annalisa, Bonaldi Laura, Mauro Francesca Romana, Scarfò Lydia, Chatzikonstantinou Thomas, Tausch Eugen, Kreuzer Karl-Anton, Kater Arnon, Bosch Francesc, Doubek Michael, Panagiotidis Panagiotis, Kalashnikova Olga, Frezzato Federica, Ruocco Valeria, Orsi Silvia, Salek Kimia, Merlo Roberto, Caregari Alberto, Glogovitis Ilias, Cellini Alessandro, Angotzi Francesco, Serafin Andrea, Yi Shuhua, Eichhorst Barbara, Woyach Jennifer A, Cuneo Antonio, Ghia Paolo, Stamatopoulos Kostas, Trentin Livio, Visentin Andrea, Bortoluzzi Stefania
Computational Genomics Group, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy.
Department of Biology, University of Padua, Padova, Italy.
J Hematol Oncol. 2025 Jul 22;18(1):74. doi: 10.1186/s13045-025-01725-y.
In Chronic Lymphocytic Leukemia (CLL), t(14;19)(q32;q13), leading to the overexpression of BCL3, is found in ∼1% of cases and is associated with an aggressive disease. In this study, leveraging a large CLL patient cohort collected thanks to an international collaboration, we investigate for the first time the circular transcriptome (circRNAome) associated with the rare t(14;19), in comparison with CLL without t(14;19) and B cells of age-matched healthy donors. We described the circRNAs commonly dysregulated in CLL, including circCSNK1G3 and circEXOC6B(3–5), which were depleted, and circZNF609 and circLPAR3, which were overexpressed in malignant cells. Of importance, we disclosed the circRNA signature of CLL with t(14;19), formed by circRNAs with expression significantly altered specifically in link with this lesion, ectopically expressed like circCDK14(3–4), circCORO1C, circCLEC2D, and circEMB, or downregulated like circCEP70(3–6). Several of these molecules were previously shown to be dysregulated or play a role in cancer, whereas most of the signature circRNAs deserve further investigation. CLL patients with high circCORO1C and circCLEC2D expression had significantly worse clinical outcomes, with shorter time to first treatment and overall survival. This study disclosed new molecular features of the aggressive CLL subtype with t(14;19).
The online version contains supplementary material available at 10.1186/s13045-025-01725-y.
在慢性淋巴细胞白血病（CLL）中，约1%的病例存在t(14;19)(q32;q13)，导致BCL3过表达，且与侵袭性疾病相关。在本研究中，借助一项国际合作收集的大量CLL患者队列，我们首次研究了与罕见t(14;19)相关的环状转录组（circRNAome），并与无t(14;19)的CLL以及年龄匹配的健康供体的B细胞进行比较。我们描述了CLL中常见的失调circRNA，包括表达减少的circCSNK1G3和circEXOC6B(3–5)，以及在恶性细胞中过表达的circZNF609和circLPAR3。重要的是，我们揭示了CLL伴t(14;19)的circRNA特征，该特征由与该病变特异性相关且表达显著改变的circRNA组成，如异位表达的circCDK14(3–4)、circCORO1C、circCLEC2D和circEMB，或下调的circCEP70(3–6)。这些分子中有几个先前已被证明在癌症中失调或发挥作用，而大多数特征性circRNA值得进一步研究。circCORO1C和circCLEC2D高表达的CLL患者临床结局明显更差，首次治疗时间和总生存期更短。本研究揭示了侵袭性CLL亚型伴t(14;19)的新分子特征。
在线版本包含可在10.1186/s13045-025-01725-y获取的补充材料。
