Author(s):
Alves, Daniela ; Ferreira, Gisela ; Caldas, Joana ; Fernandes, Mariana ; Gaspar, Cátia ; Alpoim, Mafalda ; Carvalhais, Inês ; Duarte, Sara ; Silva, Helena ; Montalvão, Ana ; Vargas, Fernanda ; Ribeiro, Teresa ; António, Ana ; Coutinho, Rita ; Miranda, Francisca ; Maia, Tânia ; Gomes, Marta ; Carda, José ; Matos, Sónia ; Jaime, Rita ; Raposo, João
Date: 2025
Persistent ID: http://hdl.handle.net/10400.17/5196
Origin: Repositório do Centro Hospitalar de Lisboa Central, EPE
Subject(s): HSAC HEM; B Lymphocytes; B-Cell Receptor; BcR; CLL; IGHV; Chronic Lymphocytic Leukemia; Immunoglobulin Heavy-Chain Variable Region Gene; Leukemia
Description
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 surpassing IGHV status. The PAIS study analyzed BcR stereotypes and IGHV mutations 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 mutated IGHV. The concentration of β2-microglobulin was significantly lower in patients with mutated IGHV (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 mutated IGHV and 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 mutated IGHV at 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.
