A review published in Frontiers in Oncology summarized the most prevalent copy number variations (CNVs) documented in patients with B-cell acute lymphoblastic leukemia (B-ALL), which offer valuable information for precise patient stratification.

Both pediatric and adult cases of B-ALL are heterogeneous and have a high incidence of a variety of CNVs, ranging from 1 Kb to 5 Mb, with uncertain clinical significance. Studies have demonstrated that between 40% to 49% of B-ALL cases carry CNVs in genes related to the regulation of early B-line cell differentiation and development, such as PAX5, IKZF1, and EBF1, and up to 60% have deletions of genes related to cell-cycle regulation, including CDKN2A/B and RB1. They have also demonstrated that 65% of pediatric B-ALL cases are associated with CNVs, particularly in IKZF1, CDKN2A/B, and PAX5.

Genes with the highest prevalence of CNVs include IKZF1, IKZF1plus (IKZF1 with additional mutations in other genes simultaneously), CDKN2A/2B, and PAX5. In B-ALL, CNVs in IKZF1 are present in 12% to 47% of pediatric cases and 6% to 84.6% of adult cases. Those characterized as IKZF1plus are present in 10% to 12.5% of pediatric cases and 14.6% to 46.4% of adult cases. CNVs in CDKN2A/2B have been identified in 25% to 41% of pediatric cases and 28.2% to 51% of adult cases. Those in PAX5 are present in 15.9% to 35% of pediatric cases and 14.6% to 46.4% of adult cases while those in CDKN2A/2B have been identified in 25% to 41% of pediatric cases and 6% to 40% of adult cases.

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Some studies have demonstrated prognostic relevance of integrated CNV profiling in B-ALL. For example, an 8-gene CNV panel for stratifying the pediatric B-ALL risk level known as the UKALL-CNV classifier, which includes IKZF1, CDKN2A/B, and PAX5 as well as PAR1, BTG1, EBF1, ETV6, and RB1. This classifier has also been used for both pediatric and adult cases and to define novel prognostic subtypes in B-ALL. Another study introduced the “MRplus” risk score system, which integrates IKZF1plus with the UKALL-CNV classifier, to better classify pediatric Ph-negative B-ALL prognosis.

In studies focused on CNVs in relapsed B-ALL clones, these genetic alterations have been correlated with proliferation and drug resistance. However, the body of literature on CNVs in relapsed B-ALL remains limited.

With the continued discovery of CNVs in B-ALL, such as in the DUX4, ZNF384, and MEF2D genes, the authors emphasized the need for consistent updating of the survival risk stratification systems and further research to help identify new prognostic markers and potential therapeutic targets.

“Nevertheless, additional multicenter survival data will be needed for further verification [of B-ALL–related copy number events and their prognostic significance] in the future,” the authors concluded in their report.


Song Y, Fang Q, Mi Y. Prognostic significance of copy number variation in B-cell acute lymphoblastic leukemia. Front Oncol. 2022;12:981036. doi:10.3389/fonc.2022.981036