Prognostic significance of copy number alterations detected by multi-link probe amplification of multiple genes in adult acute lymphoblastic leukemia.

The multiplex ligation-dependent probe amplification (MLPA) method was used to detect the copy number alterations (CNAs) of IKAROS family zinc finger 1 ( IKZF1 ), paired box 5 ( PAX5 ), ETS variant 6 ( ETV6 ), RB transcriptional corepressor 1 ( RB1 ), BTG anti-proliferation factor 1 ( BTG1 ), early B-cell factor 1 ( EBF1 ), cyclin dependent kinase inhibitor 2A/2B ( CDKN2A/2B ) and cytokine receptor like factor 2 ( CRLF2 ) genes in 87 adults with acute lymphoblastic leukemia (ALL) in China. The effects of CNAs on prognosis were analyzed. Gene deletions were detected in 58/87 (66.7%) ALL patients. The most common deletions were observed in the following genes: IKZF1 (40.6%), CDKN2A (31.9%), CDKN2B (29%), PAX5 (21.7%), RB1 (14.5%) and BTG1 (10.1%). B cell-ALL (B-ALL) patients with CDKN2A/2B deletions exhibited poor 2-year overall survival (OS; P=0.055) and relapse-free survival (RFS; P=0.054) rates. CDKN2A/2B deletions were associated with poor 2-year OS (P=0.045) and RFS (P=0.071) rates in Philadelphia chromosome positive (Ph+ ) B-ALL patients, as well as in the high risk (HR) B-ALL group (P=0.037 and P=0.047, respectively). Patients with PAX5 deletions displayed poor 2-year OS (P=0.004) and RFS (P=0.016) rates in Philadelphia chromosome negative (Ph- ) B-ALL patients. Patients with ≥3 gene deletions exhibited a poorer prognosis than other patients (OS, P=0.001; RFS, 0.002).