Background/Objectives: Chronic lymphocytic leukemia (CLL) exhibits a heterogeneous clinical course influenced by genetic factors, such as the mutational status of immunoglobulin variable regions (IGHV). Recently, B-cell receptor (BcR) stereotypes have shown promising prognostic value, potentially surpassingIGHVstatus. The PAIS study analyzed BcR stereotypes andIGHVmutations in newly diagnosed Portuguese CLL patients to assess prognostic characteristics and disease progression. Methods: This cross-sectional study included 463 adult patients from 15 Portuguese centers, recruited between November 2020 and September 2023. The median age at diagnosis was 70.4 years. The most common clinical stages were 0 (54%) and 1 (32.83%). Results: A total of 15 different BcR stereotypes were identified in the cohort studied. Subtype #1, associated with a poorer prognosis, was the most prevalent, observed in 3.90% of newly diagnosed Portuguese CLL patients. Considering the 19 major stereotypes that could be assigned by the ARResT subsets tool, most patients exhibited a heterogeneous BcR profile (90.14%). A total of 57.24% of patients had mutatedIGHV. The concentration of β2-microglobulin was significantly lower in patients with mutatedIGHV(2.6 mg/L vs. 3.6 mg/L,p< 0.001). Clinical stage, assessed by the RAI staging system, differed between subgroups, with a higher frequency of stage 0 in patients with mutatedIGHVand stage 2 in unmutated patients (p= 0.009). Conclusions: The PAIS study highlighted the predominance of a heterogeneous BcR profile in Portuguese CLL patients. The higher percentage of patients with mutatedIGHVat diagnosis supports prior findings. This study improves the characterization of the 10% of Portuguese CLL patients with major BcR stereotypes, offering healthcare providers better predictive power for disease progression and potentially impacting clinical decision making.
背景/目的：慢性淋巴细胞白血病（CLL）的临床病程具有异质性，受免疫球蛋白可变区（IGHV）突变状态等遗传因素影响。近年来，B细胞受体（BcR）模式化特征显示出超越IGHV状态的潜在预后价值。PAIS研究通过分析新诊断葡萄牙CLL患者的BcR模式化特征及IGHV突变，评估其预后特征与疾病进展。方法：这项横断面研究纳入2020年11月至2023年9月期间葡萄牙15个中心的463例成年患者，诊断时中位年龄70.4岁。最常见临床分期为0期（54%）和1期（32.83%）。结果：在研究队列中共鉴定出15种不同的BcR模式化特征。其中预后较差的#1亚型最为常见，占新诊断葡萄牙CLL患者的3.90%。通过ARResT亚型分析工具可识别的19种主要模式化特征中，多数患者呈现异质性BcR谱（90.14%）。57.24%的患者存在IGHV突变。突变型IGHV患者的β2-微球蛋白浓度显著更低（2.6 mg/L vs. 3.6 mg/L，p<0.001）。RAI分期系统评估显示，临床分期在亚组间存在差异：突变型IGHV患者中0期比例更高，未突变患者中2期比例更高（p=0.009）。结论：PAIS研究揭示了葡萄牙CLL患者以异质性BcR谱为主的特征。诊断时较高比例的IGHV突变患者与既往研究一致。本研究深化了对10%具有主要BcR模式化特征的葡萄牙CLL患者的认识，为医疗从业者提供了更精准的疾病进展预测依据，可能对临床决策产生影响。
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