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Abstract：
Immunoglobulin heavy chain variable ( IGHV ) region mutations, TP53 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 IGHV 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, p < 0.0001), and shorter OS (112 vs. 246 months, p < 0.0001) than the mutated CLL. IGHV3 was the most frequently used IGHV family (46%), followed by IGHV1 (30%) and IGHV4 (16%). IGHV5-51 and IGHV1-69 subfamilies were associated with poor prognosis, while IGHV4 and IGHV2 showed the best outcomes. The prevalence of CK was 15% and was significantly associated with U-CLL. In the multivariable analysis, IGHV2 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, IGHV and TP53 mutations, IGHV gene families, and CK information could help clinicians in the decision-making process.
摘要：
免疫球蛋白重链可变区突变,TP53突变,荧光原位杂交（FISH），在我们的日常实践中，细胞遗传学分析是慢性淋巴细胞白血病（CLL）患者最重要的预后生物标志物。在现实生活中,很少有研究分析这些因素与结果的相关性，主要指首次治疗时间（TTFT）和总生存期（OS）。本研究旨在表征IGHV突变状态，家庭使用,FISH畸变,和复杂核型（CK），并分析TTFT和OS对西班牙队列375例CLL患者的预后影响。我们发现未突变的CLL（U-CLL）与更具侵袭性的疾病有关，较短的TTFT(48vs.133个月,p<0.0001),和较短的操作系统(112与246个月,p<0.0001)比突变的CLL。IGHV3是最常用的IGHV家族（46%），其次是IGHV1（30％）和IGHV4（16％）。IGHV5-51和IGHV1-69亚家族与不良预后相关。而IGHV4和IGHV2显示最佳结果。CK的患病率为15％，与U-CLL显着相关。在多变量分析中，IGHV2基因使用和del13q与较长的TTFT相关，而VH1-02,+12,del11q,del17p,和U-CLL与较短的TFT。此外，VH1-69用法，del11q,del17p,U-CLL与较短的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细胞遗传学畸变，IGHV和TP53突变，IGHV基因家族,和CK信息可以帮助临床医生在决策过程中。
