Frontiers in Oncology (Apr 2024)

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

  • Joaquin Garcia-Solorio,
  • Juan Carlos Núñez-Enriquez,
  • Marco Jiménez-Olivares,
  • Janet Flores-Lujano,
  • Fernanda Flores-Espino,
  • Carolina Molina-Garay,
  • Alejandra Cervera,
  • Diana Casique-Aguirre,
  • Diana Casique-Aguirre,
  • José Gabriel Peñaloza-Gonzalez,
  • Ma. Del Rocío Baños-Lara,
  • Ángel García-Soto,
  • César Alejandro Galván-Díaz,
  • Alberto Olaya-Vargas,
  • Hilario Flores Aguilar,
  • Minerva Mata-Rocha,
  • Miguel Ángel Garrido-Hernández,
  • Juan Carlos Solís-Poblano,
  • Nuria Citlalli Luna-Silva,
  • Lena Sarahi Cano-Cuapio,
  • Pierre Mitchel Aristil-Chery,
  • Fernando Herrera-Quezada,
  • Karol Carrillo-Sanchez,
  • Anallely Muñoz-Rivas,
  • Luis Leonardo Flores-Lagunes,
  • Elvia Cristina Mendoza-Caamal,
  • Beatriz Eugenia Villegas-Torres,
  • Vincent González-Osnaya,
  • Elva Jiménez-Hernández,
  • José Refugio Torres-Nava,
  • Jorge Alfonso Martín-Trejo,
  • María de Lourdes Gutiérrez-Rivera,
  • Rosa Martha Espinosa-Elizondo,
  • Laura Elizabeth Merino-Pasaye,
  • María Luisa Pérez-Saldívar,
  • Silvia Jiménez-Morales,
  • Everardo Curiel-Quesada,
  • Haydeé Rosas-Vargas,
  • Juan Manuel Mejía-Arangure,
  • Juan Manuel Mejía-Arangure,
  • Carmen Alaez-Verson

DOI
https://doi.org/10.3389/fonc.2024.1337954
Journal volume & issue
Vol. 14

Abstract

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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.

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