Landscape of Genetic Alterations and Their Clinical Impacts in Pediatric B-Cell Acute Lymphoblastic Leukemia: A Single Centre Experience

Abstract

Background. IKZF1 gene deletions have been identified as a poor prognostic factor in pediatric B-cell acute lymphoblastic leukemia (B-ALL), especially in the presence of co-occurring deletions (IKZF1^plus profile). This study aimed to determine the frequency of IKZF1 deletions and deletions in other B-cell differentiation and cell cycle control genes, and their prognostic impact in Slovenian pediatric B-ALL patients.

Patients and methods. We studied a cohort of 99 patients diagnosed with B-ALL from January 2012 to December 2020 and treated according to the ALL IC-BFM 2009 protocol. Ninety-one bone marrow or peripheral blood samples were analysed for copy number variations (CNVs) using the SALSA MLPA P335 ALL-IKZF1 probemix.

Results. At least one CNV was detected in more than 65% of analysed samples, and the most frequent were alterations in PAX5 and CDKN2A/B. Deletions in IKZF1 were present in 17.6% of analysed samples and were associated with an inferior 5-year event-free survival (EFS; 54.8% vs. 86.7%, p = 0.011). The IKZF1^plus profile was identified in 12% of the analysed samples, and these patients had an inferior 5-year EFS than those with deletions in IKZF1 only and those without deletions (50.8% vs. 75.0% vs. 86.7%, respectively, p = 0.035). Overall survival was also worse in patients with the IKZF1^plus profile. However, the difference between the groups was not statistically significant.

Conclusions. Our results are in concordance with the results obtained in larger cooperative clinical trials. Copy number variations analysis using the SALSA MLPA kit is a reliable tool for initial diagnostic approach in children with B-ALL, even in smaller institutions in low- and middle-income countries.