Mollstedt John, Mansouri Larry, Rosenquist Richard
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Clinical Genetics, Karolinska University Hospital, Solna, Sweden.
Front Oncol. 2023 Mar 21;13:1146486. doi: 10.3389/fonc.2023.1146486. eCollection 2023.
Genetic diagnostics of hematological malignancies has evolved dramatically over the years, from chromosomal banding analysis to next-generation sequencing, with a corresponding increased capacity to detect clinically relevant prognostic and predictive biomarkers. In diagnostics of patients with chronic lymphocytic leukemia (CLL), we currently apply fluorescence hybridization (FISH)-based analysis to detect recurrent chromosomal aberrations (del(11q), del(13q), del(17p) and trisomy 12) as well as targeted sequencing (IGHV and mutational status) for risk-stratifying purposes. These analyses are performed before start of any line of treatment and assist in clinical decision-making including selection of targeted therapy (BTK and BCL2 inhibitors). Here, we present the current view on the genomic landscape of CLL, including an update on recent advances with potential for clinical translation. We discuss different state-of-the-art technologies that are applied to enable precision diagnostics in CLL and highlight important genomic markers with current prognostic and/or predictive impact as well as those of prospective clinical relevance. In the coming years, it will be important to develop more comprehensive genomic analyses that can capture all types of relevant genetic aberrations, but also to develop highly sensitive assays to detect minor mutations that affect therapy response or confer resistance to targeted therapies. Finally, we will bring up the potential of new technologies and multi-omics analysis to further subclassify the disease and facilitate implementation of precision medicine approaches in this still incurable disease.
多年来，血液系统恶性肿瘤的基因诊断技术取得了巨大进展，从染色体显带分析发展到新一代测序，检测临床相关预后和预测生物标志物的能力相应提高。在慢性淋巴细胞白血病（CLL）患者的诊断中，我们目前采用基于荧光原位杂交（FISH）的分析方法来检测复发性染色体畸变（11q缺失、13q缺失、17p缺失和三体12），以及用于风险分层的靶向测序（IGHV和突变状态）。这些分析在任何治疗线开始前进行，有助于临床决策，包括靶向治疗（BTK和BCL2抑制剂）的选择。在此，我们阐述了CLL基因组格局的当前观点，包括对具有临床转化潜力的最新进展的更新。我们讨论了用于实现CLL精准诊断的不同前沿技术，并强调了具有当前预后和/或预测影响以及具有前瞻性临床相关性的重要基因组标志物。在未来几年，开发能够捕获所有类型相关基因畸变的更全面基因组分析，以及开发高度灵敏的检测方法来检测影响治疗反应或导致对靶向治疗耐药的微小突变将非常重要。最后，我们将探讨新技术和多组学分析在进一步对该疾病进行亚分类以及促进在这种仍无法治愈的疾病中实施精准医学方法方面的潜力。
