INFLUENCE OF IKZF1 GENETIC VARIANTS ON THE SUSCEPTIBILITY AND PROGNOSIS OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

Victoria Fernanda Lima Mendes, Larissa Joanny Alkmin, Manoella Marchezini Camargo Penteado,
Marla Karine Amarante, Carlos Eduardo Coral de Oliveira

ABSTRACT

Introduction: Acute lymphoblastic leukemia accounts for about 75% of childhood cancers. The development of the disease results from interactions between genetic and environmental factors; however, susceptibility in children and adolescents is still not fully understood. The transcription factor IKAROS, encoded by the IKZF1 gene, regulates lymphocyte development, and its genetic variants are common in ALL and associated with higher relapse risk. Objective: To evaluate the genetic polymorphisms rs4132601 and rs10272724 of the IKZF1 gene and their relationship with susceptibility and prognosis in children with ALL. Materials and Methods: DNA samples from 59 patients diagnosed with ALL at the Londrina Cancer Hospital were analyzed. Variants were assessed after DNA amplification by polymerase chain reaction and genotyping by restriction fragment length polymorphism. Prognostic parameters were evaluated, and case-control association tests were performed. Results: No variant showed an association with susceptibility to ALL (p>0.05). However, the rs10272724 variant correlated with a poorer treatment response (ρ=0.288; p=0.047) and a higher risk of death (ρ=0.301; p=0.024), regardless of ALL subtype or relapse. The rs4132601 variant showed a moderate correlation with an increased risk of relapse (ρ=0.520; p=0.001), but not with disease classification, treatment response, or mortality. Conclusion: Although any variants were not associated with susceptibility to ALL, the polymorphisms analyzed showed an association with relevant prognostic parameter, such as treatment response, relapse, and chance of death. The findings support the hypothesis that IKZF1 gene variants may have prognostic value in childhood acute lymphoblastic leukemia, contributing to more individualized treatments and advances in oncohematology.

Keywords: Acute lymphoblastic leukemia; IKAROS transcription factor; Gene variants; Disease susceptibility; Cancer prognosis.