<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec id="j_raon-2021-0050_s_005">
<h3>Background</h3>
<p><italic>IKZF1</italic> 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 (<italic>IKZF1</italic><sup>plus</sup> profile). This study aimed to determine the frequency of <italic>IKZF1</italic> deletions and deletions in other B-cell differentiation and cell cycle control genes, and their prognostic impact in Slovenian pediatric B-ALL patients.</p>
</sec>
<sec id="j_raon-2021-0050_s_006">
<h3>Patients and methods</h3>
<p>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. Eighty-eight bone marrow or peripheral blood samples were analysed for copy number variations (CNVs) using the SALSA MLPA P335 ALL-IKZF1 probemix.</p>
</sec>
<sec id="j_raon-2021-0050_s_007">
<h3>Results</h3>
<p>At least one CNV was detected in more than 65% of analysed samples. The most frequently altered genes were <italic>PAX5</italic> and <italic>CDKN2A/B</italic> (30.7%, 26.1%, and 25.0%, respectively). Deletions in <italic>IKZF1</italic> were present in 18.2% of analysed samples and were associated with an inferior 5-year event-free survival (EFS; 54.8% <italic>vs</italic>. 85.9%, p = 0.016). The <italic>IKZF1</italic><sup>plus</sup> profile was identified in 12.5% of the analysed samples, and these patients had an inferior 5-year EFS than those with deletions in <italic>IKZF1</italic> only and those without deletions (50.8% <italic>vs</italic>. 75.0% <italic>vs</italic>. 85.9%, respectively, p = 0.049). Overall survival (OS) was also worse in patients with the <italic>IKZF1</italic><sup>plus</sup> profile than those with deletions in <italic>IKZF1</italic> only and those without deletions (5-year OS 76.2% <italic>vs</italic>. 100% <italic>vs</italic>. 93.0%, respectively). However, the difference between the groups was not statistically significant.</p>
</sec>
<sec id="j_raon-2021-0050_s_008">
<h3>Conclusions</h3>
<p>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.</p>
</sec>
</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 (IKZF1plus 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. Eighty-eight 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. The most frequently altered genes were PAX5 and CDKN2A/B (30.7%, 26.1%, and 25.0%, respectively). Deletions in IKZF1 were present in 18.2% of analysed samples and were associated with an inferior 5-year event-free survival (EFS; 54.8% vs. 85.9%, p = 0.016). The IKZF1plus profile was identified in 12.5% 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. 85.9%, respectively, p = 0.049). Overall survival (OS) was also worse in patients with the IKZF1plus profile than those with deletions in IKZF1 only and those without deletions (5-year OS 76.2% vs. 100% vs. 93.0%, respectively). 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.

Clinical impacts of copy number variations in B-cell differentiation and cell cycle control genes in pediatric B-cell acute lymphoblastic leukemia: a single centre experience

Radiology and Oncology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Background
IKZF1 gene deletions have been identified as a poor prognostic factor in pediatric B-cell acute lymphoblastic leukemia (B-ALL), especially in the...

Clinical impacts of copy number variations in B-cell differentiation and cell cycle control genes in pediatric B-cell acute lymphoblastic leukemia: a single centre experience

Article Category: Research Article

Published Online: Dec 22, 2021

Page range: 92 - 101

Received: Sep 07, 2021

Accepted: Nov 05, 2021

DOI: https://doi.org/10.2478/raon-2021-0050

© 2022 Klementina Crepinsek, Gasper Marinsek, Marko Kavcic, Tomaž Prelog, Lidija Kitanovski, Janez Jazbec, Marusa Debeljak, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.