Muñoz-Novas Carolina, González-Gascón-Y-Marín Isabel, Figueroa Iñigo, Sánchez-Paz Laura, Pérez-Carretero Claudia, Quijada-Álamo Miguel, Rodríguez-Vicente Ana-Eugenia, Infante María-Stefania, Foncillas María-Ángeles, Landete Elena, Churruca Juan, Marín Karen, Ramos Victoria, Sánchez Salto Alejandro, Hernández-Rivas José-Ángel
Servicio de Hematología, Hospital Universitario Infanta Leonor, Madrid, Spain.
Departamento de Medicina, Universidad Complutense, Madrid, Spain.
Glob Med Genet. 2024 Feb 12;11(1):59-68. doi: 10.1055/s-0044-1779668. eCollection 2024 Jan.
Immunoglobulin heavy chain variable ( ) region mutations, mutation, fluorescence in situ hybridization (FISH), and cytogenetic analysis are the most important prognostic biomarkers used in chronic lymphocytic leukemia (CLL) patients in our daily practice. In real-life environment, there are scarce studies that analyze the correlation of these factors with outcome, mainly referred to time to first treatment (TTFT) and overall survival (OS). This study aimed to typify mutation status, family usage, FISH aberrations, and complex karyotype (CK) and to analyze the prognostic impact in TTFT and OS in retrospective study of 375 CLL patients from a Spanish cohort. We found unmutated CLL (U-CLL) was associated with more aggressive disease, shorter TTFT (48 vs. 133 months, < 0.0001), and shorter OS (112 vs. 246 months, < 0.0001) than the mutated CLL. was the most frequently used family (46%), followed by (30%) and (16%). and subfamilies were associated with poor prognosis, while and showed the best outcomes. The prevalence of CK was 15% and was significantly associated with U-CLL. In the multivariable analysis, gene usage and del13q were associated with longer TTFT, while VH1-02, +12, del11q, del17p, and U-CLL with shorter TTFT. Moreover, VH1-69 usage, del11q, del17p, and U-CLL were significantly associated with shorter OS. A comprehensive analysis of genetic prognostic factors provides a more precise information on the outcome of CLL patients. In addition to FISH cytogenetic aberrations, and mutations, gene families, and CK information could help clinicians in the decision-making process.
免疫球蛋白重链可变（ ）区突变、 突变、荧光原位杂交（FISH）和细胞遗传学分析是我们日常临床实践中用于慢性淋巴细胞白血病（CLL）患者最重要的预后生物标志物。在现实环境中，很少有研究分析这些因素与预后的相关性，主要涉及首次治疗时间（TTFT）和总生存期（OS）。本研究旨在对 突变状态、家族使用情况、FISH异常和复杂核型（CK）进行分类，并在一项对来自西班牙队列的375例CLL患者的回顾性研究中分析其对TTFT和OS的预后影响。我们发现，与突变型CLL相比，未突变CLL（U-CLL）与更具侵袭性的疾病、更短的TTFT（48个月对133个月， ＜0.0001）和更短的OS（112个月对246个月， ＜0.0001）相关。 是最常用的 家族（46%），其次是 （30%）和 （16%）。 和 亚家族与不良预后相关，而 和 显示出最佳预后。CK的患病率为15%，且与U-CLL显著相关。在多变量分析中， 基因使用和del13q与更长的TTFT相关，而VH1-02、+12、del11q、del17p和U-CLL与更短的TTFT相关。此外，VH1-69使用、del11q、del17p和U-CLL与更短的OS显著相关。对遗传预后因素的综合分析为CLL患者的预后提供了更精确的信息。除了FISH细胞遗传学异常、 和 突变外， 基因家族和CK信息可以帮助临床医生进行决策。
