ALL-545 Is the Distribution of Gene Copy Number Alteration in Ph-Positive B-ALL Different From Ph-Negative B-ALL?

Abstract

Context The copy number alterations (CNAs) in B-ALL, particularly IKZF1 deletions, can have significant implications for disease prognosis and may also lead to resistance to therapy. Objective To establish and compare the prevalence of CNAs in Ph-positive B-ALL and Ph-negative B-ALL. Study Design Genomic DNA and total RNA were obtained from the peripheral blood or bone marrow. Multiplex RT-PCR was done for recurrent translocations including BCR::ABL1. CNAs in B-cell differentiation and cell cycle control genes (EBF1, CDKN2A/B, PAX5, ETV6, BTG1 and RB1) and in the PAR1 region were detected by multiplex ligation-dependent probe amplification (MLPA) using P335 kit (MRC, Holland). Results A total of 189 B-ALL patients were categorized into Ph-positive (43; 22.75%) and Ph-negative (146; 77.25%). The median age of the patients was 15 years (8 months–61 years); Ph-positive cases–31 years (2–60 years) and Ph-negative–13 years (8 months–61 years). The CNAs in the overall cohort were detected in 133 (70.4%) cases; the most commonly altered genes were IKZF1–63 (33.3%), CDKN2A/B-59 (31.2%), and PAX5-56 (29.63%). The commonly altered genes in the Ph-positive group were IKZF1–30 (69.8%), PAX5–16 (37.2%), and CDKN2A/B–15 (34.9%); and in the Ph-negative group: CDKN2A/B–44 (30.1%), PAX5–40 (27.4%), and IKZF1–33 (22.6%). The patients were grouped into three categories, with CNA in 1 gene–51 cases (27%), 2 genes–36 cases (19%), and >=3 genes–46 cases (24%). The Ph-positive cohort had 12 cases (27.9%), 10 cases (23.25%), and 16 cases (37.2%) with CNAs in 1 gene, 2 genes, and >=3 genes, respectively; the Ph-negative cohort had 39 cases (26.7%), 26 cases (17.8%), and 30 cases (20.5%) with CNAs in 1, 2, and >=3 genes, respectively. Conclusions Our study indicates that the CNAs in Ph-positive B-ALL differ from that of Ph-negative B-ALL. The most affected gene in the Ph-positive B-ALL cohort was IKZF1 compared to CDKN2A/B in the Ph-negative cases. The Ph-positive cohort overall had CNAs in a higher number of genes (>=3 genes–37.2% of cases) than the Ph-negative cohort (20.5%), possibly indicating a higher genomic susceptibility in Ph-positive B-ALL.