IKZF1 Deletions as a Prognostic Factor in Costa Rican Patients With Pediatric B-Cell Acute Lymphoblastic Leukemia

The IKZF1 gene encodes for Ikaros, a transcriptional factor in B-cell development. Deletions in this gene have been associated with a worse prognosis in B-cell acute lymphoblastic leukemia (B-ALL). We evaluated the presence of these alterations in all Costa Rican pediatric patients diagnosed with B-ALL between 2011 and 2014, treated with a modified Berlin-Frankfurt-Münster therapeutic protocol. Multiplex polymerase chain reaction with 2 detection methods (agarose gel and gene scanning) was used to detect intragenic deletions and multiplex ligation-dependent probe amplification for whole-gene deletions. Differences between groups (normal vs. deleted IKZF1) were analyzed by the χ test, the Kaplan-Meier test was used to calculate relapse-free survival and overall survival, and Cox regression was performed for multivariant analysis. Minimum follow-up was 4.5 years. Incidence of IKZF1 deletions was 12.9% (n=20), with an equal amount of intragenic and complete gene deletions. Adverse karyotype (P=0.048), high-risk category (P=0.030), occurrence of relapse (P=0.021), and medullar relapse (P=0.011) were statistically associated with the presence of deletions in IKZF1. Relapse-free survival at 54 months was lower in patients harboring an IKZF1 deletion than that in patients with IKZF1-wt (40.0% vs. 66.7%; P=0.014). Patients with B-ALL and IKZF1 deletions, showed a poorer relapse-free survival, in comparison with patients with IKZF1-wt, suggesting that IKZF1 status is an independent prognostic factor for pediatric patients with B-ALL.