ALL-544 exploring the genetic landscape of B-ALL: A comparative analysis of copy number alterations in adult and pediatric B-ALL patients

Abstract

Context: B-cell acute lymphoblastic leukemia (B-ALL) primarily affects the pediatric and young adult populations. Generally, pediatric patients have better prognostic outcomes compared to adults. However, there is a lack of comparative data on copy number alterations (CNAs) in adult and pediatric B-ALL patients. Objective: To study the genetic landscape or CNAs of B-ALL in adult and pediatric B-ALL patients. Study Design: Overall, 214 B-ALL patients were enrolled and divided into pediatric (≤18 years) and adult (≥19 years) cohorts for comparison. Genomic DNA from bone marrow/peripheral blood samples underwent multiplex ligation-dependent probe amplification (MLPA) for CNAs using P335 kit (MRC, Holland). The CNAs of key genes were detected, namely EBF1, IKZF1, JAK2, CDKN2A, CDKN2B, PAX5, ETV6, BTG1, RB1 and the Xp22.33/Yp11.31 region (PAR1), comprising CRLF2, CSF2RA, and IL3RA. Results: The analysis incorporated a cohort of 214 patients comprising 126 (58.8%) pediatric and 88 (41.2%) adult cases diagnosed with B-ALL. Patients in the adult cohort had a median age of 33.5 years (range 19–61 years), and patients in the pediatric cohort had a median age of 7 years (range 8mths–18 years). CNAs were identified in a total of 148 cases (69.1%) in our study. The most frequently affected genes associated with CNAs were CDKN2A/B, observed in 71 cases (33.1%), IKZF1–68 cases (31.7%), and PAX5–65 cases (30.3%). Among the patients in the pediatric cohort, the most affected genes were CDKN2A/B–37 cases (29.3%), PAX5–30 cases (23.8%), and IKZF1–21 cases (16.6%). In the adult group, the most frequently affected genes were IKZF1–47 cases (53.4%), CDKN2A/B–34 cases (38.4%), and PAX5–35 cases (39.7%). The pediatric cohort had 35 (28%), 20 (16%), 20 (16%) cases with 1, 2, and ≥3 CNAs, respectively, and the adult cohort had 22(25%), 17(19%), and 34 (39%) cases, respectively. Conclusion Our findings indicate an overall higher proportion of >3CNAs (39% vs 16%) in the adult B-ALL patients as well as much higher prevalence of IKZF1 deletions (53.4% vs 16.6%).