Analysis of Stereotyped B-Cell Receptor Frequencies Among Portuguese De Novo-Diagnosed Chronic Lymphocytic Leukemia Patients (PAIS Study)
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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.
Source: Cancers
Authors: Daniela Alves, Gisela Ferreira, Joana Caldas, Mariana Fernandes, Cátia Gaspar, Mafalda Alpoim, Inês Carvalhais, Sara Duarte, Helena Silva, Ana Montalvão, Fernanda Vargas, Teresa Ribeiro, Ana António, Rita Coutinho, Francisca Miranda, Tânia Maia, Marta Gomes, José Carda, Sónia Matos, Rita Jaime, João Raposo
Institutions: Unidade Local de Saúde Santa Maria, Unidade Local de Saúde da Região de Aveiro, Unidade Local de Saúde de São José, Hospital Santo António dos Capuchos, Unidade Local de Saúde Gaia/Espinho, Hospital de São João, Unidade Local de Saúde de Coimbra, Hospital São Teotónio, Unidade Local de Saúde de Viseu Dão-Lafões, Unidade Local de Saúde do Baixo Alentejo, Hospital Garcia de Orta, Unidade Local de Saúde de Almada-Seixal, Hospital Braga, Unidade Local de Saúde de Braga, Unidade Local de Saúde da Arrábida, Hospital de Santo António, Unidade Local de Saúde de Santo António EPE, Hospital of St. Francis Xavier, Hospital Pedro Hispano, Unidade Local de Saúde de Matosinhos, Hospital da Luz, Johnson & Johnson (United States)
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Funder: Johnson and Johnson
Award: G5251202341
OpenAlex ID: W4409409494