Polaskova Kristyna, Merta Tomas, Martincekova Alexandra, Zapletalova Danica, Kyr Michal, Mazanek Pavel, Krenova Zdenka, Mudry Peter, Jezova Marta, Tuma Jiri, Skotakova Jarmila, Cervinkova Ivana, Valik Dalibor, Zdrazilova-Dubska Lenka, Noskova Hana, Pal Karol, Slaby Ondrej, Fabian Pavel, Kozakova Sarka, Neradil Jakub, Veselska Renata, Kanderova Veronika, Hrusak Ondrej, Freiberger Tomas, Klement Giannoula Lakka, Sterba Jaroslav
Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czechia.
International Clinical Research Center, St. Anne's University Hospital, Brno, Czechia.
Front Oncol. 2020 Feb 7;9:1531. doi: 10.3389/fonc.2019.01531. eCollection 2019.
In order to identify reasons for treatment failures when using targeted therapies, we have analyzed the comprehensive molecular profiles of three relapsed, poor-prognosis Burkitt lymphoma cases. All three cases had resembling clinical presentation and histology and all three patients relapsed, but their outcomes differed significantly. The samples of their tumor tissue were analyzed using whole-exome sequencing, gene expression profiling, phosphoproteomic assays, and single-cell phosphoflow cytometry. These results explain different treatment responses of the three histologically identical but molecularly different tumors. Our findings support a personalized approach for patient with high risk, refractory, and rare diseases and may contribute to personalized and customized treatment efforts for patients with limited treatment options like relapsed/refractory Burkitt lymphoma.
The main aim of this study is to analyze three relapsed Burkitt lymphoma patients using a comprehensive molecular profiling, in order to explain their different outcomes and to propose a biomarker-based targeted treatment. In cases 1 and 3, the tumor tissue and the host were analyzed prospectively and appropriate target for the treatment was successfully implemented; however, in case 2, analyses become available only retrospectively and his empirically based rescue treatment did not hit the right target of his disease.
为了确定使用靶向治疗时治疗失败的原因，我们分析了3例复发、预后不良的伯基特淋巴瘤病例的综合分子特征。所有3例病例临床表现和组织学相似，且均复发，但结局差异显著。对其肿瘤组织样本进行了全外显子组测序、基因表达谱分析、磷酸化蛋白质组学检测和单细胞磷酸化流式细胞术分析。这些结果解释了这3例组织学相同但分子特征不同的肿瘤的不同治疗反应。我们的研究结果支持对高危、难治性和罕见疾病患者采用个性化方法，可能有助于为复发/难治性伯基特淋巴瘤等治疗选择有限的患者开展个性化和定制化治疗工作。
本研究的主要目的是通过综合分子特征分析3例复发的伯基特淋巴瘤患者，以解释其不同结局并提出基于生物标志物的靶向治疗方案。在病例1和病例3中，对肿瘤组织和宿主进行了前瞻性分析，并成功实施了合适的治疗靶点；然而，在病例2中，分析仅为回顾性，其基于经验的挽救治疗未命中疾病的正确靶点。
