IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia

• Published in: Frontiers in oncology 2024-04, Vol.14, p.1337954-1337954
• Main Authors: Garcia-Solorio, Joaquin, Núñez-Enriquez, Juan Carlos, Jiménez-Olivares, Marco, Flores-Lujano, Janet, Flores-Espino, Fernanda, Molina-Garay, Carolina, Cervera, Alejandra, Casique-Aguirre, Diana, Peñaloza-Gonzalez, José Gabriel, Baños-Lara, Ma. Del Rocío, García-Soto, Ángel, Galván-Díaz, César Alejandro, Olaya-Vargas, Alberto, Aguilar, Hilario Flores, Mata-Rocha, Minerva, Garrido-Hernández, Miguel Ángel, Solís-Poblano, Juan Carlos, Luna-Silva, Nuria Citlalli, Cano-Cuapio, Lena Sarahi, Aristil-Chery, Pierre Mitchel, Herrera-Quezada, Fernando, Carrillo-Sanchez, Karol, Muñoz-Rivas, Anallely, Flores-Lagunes, Luis Leonardo, Mendoza-Caamal, Elvia Cristina, Villegas-Torres, Beatriz Eugenia, González-Osnaya, Vincent, Jiménez-Hernández, Elva, Torres-Nava, José Refugio, Martín-Trejo, Jorge Alfonso, Gutiérrez-Rivera, María de Lourdes, Espinosa-Elizondo, Rosa Martha, Merino-Pasaye, Laura Elizabeth, Pérez-Saldívar, María Luisa, Jiménez-Morales, Silvia, Curiel-Quesada, Everardo, Rosas-Vargas, Haydeé, Mejía-Arangure, Juan Manuel, Alaez-Verson, Carmen
• Format: Article
• Language: English
• Subjects: CDKN2A/2B gene mutation; IKZF1 gene mutation; IKZF1plus; Oncology; PAR1 deletions; PAX5 gene mutation; pediatric B-ALL
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2024.1337954

BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.