Gene Deletions and Prognostic Values in B-Linage Acute Lymphoblastic Leukemia

Abstract

Although pediatric-like treatment regimen has remarkably improved the survival rates of adults with acute lymphoblastic leukemia (ALL), the outcome of some adult patients is still poor owing to adverse genetic features. These molecular abnormalities, especially gene deletions, may be considered for the prognosis assessment for adult patients with ALL. In this study, using multiplex ligation-dependent probe amplification (MLPA) method, gene deletions were analyzed in from 211 adult B-ALL patients treated in our center. The data showed that 68.2% (144/211) adult B-ALL patients carried gene deletions, and the frequency is much higher in Ph+B-ALL patients. IKZF1 gene deletion is the most common gene deletion in adult B-ALL, followed by CDKN2A/B deletion. In Ph-B-ALL patients, the overall survival of patients with gene deletions is inferior to that of patients without any gene deletions. More obviously, patients with IKZF1 or CDKN2A/B deletion had a worse prognosis, whereas, allogeneic hematopoietic stem cell transplantation could improve OS in patients with IKZF1 deletion, but not in patients with CDKN2A/B deletion. Moreover, the outcome of Ph-B-ALL patients with double deletion of IKZF1and CDKN2A/B may be much worse than that of patients with IKZF1 or CDKN2A/B alone. Minimal residual disease (MRD) was also analyzed together with gene deletions and demonstrated that gene deletions have a negative impact on survival only in MRD positive Ph-B-ALL patients. In conclusion, gene deletions are closely related with the prognosis of adult Ph-B-ALL patients.

Prognostic significance of copy number variation in B-cell acute lymphoblastic leukemia

“…As shown in Table 1 , PAX5 deletions occurred in 15.9%–31.7% of pediatric Ph− B-ALL, 33% of pediatric Ph+ B-ALL ( 14 ), 27.1%–40% of adult Ph+ B-ALL, and 22.9%–23.8% of adult Ph-B-ALL (31.8%–38% Ph-like ALL) cases. No statistical difference has been reported between adult Ph− B-ALL and Ph+ B-ALL (27.1% vs. 27.8%, P = 0.549) cases ( 5 ). Most PAX5 deletions coexisted with CDKN2A/B deletions (83.3% of children and 100.0% of adults) and were commonly deleted in ETV6-RUNX1 B-ALL.…”

“…The frequency of adult CDKN2A/B deletions in the Ph-B-ALL group was much higher than in the Ph+ B-ALL group (39.7% vs. 24.7%, P = 0.041) ( 5 ). The prognostic value of CDKN2A/B in adults has been debated previously ( 35 , 41 , 44 ).…”

“…CNVs are frequently detected in B-ALL with considerable heterogeneity distribution ( 34 ). Overall, about 40%–49% of B-ALL carried gene CNVs that regulate early B-line cell differentiation and development-related genes (e.g., PAX5 , IKZF1 , and EBF1 ) and about 60% carry deletions of cell-cycle regulatory genes (e.g., CDKN2A/B and RB1 ) ( 5 , 14 ). Broadly, CNVs occurred in 65% of pediatric B-ALL cases ( 35 ).…”

“…In adult B-ALL, IKZF1 deletions were detected about 70% of Ph+ B-ALL cases ( 4 , 5 ), around 15%–30% of Ph− B-ALL ( 53 ), and 40% of Ph-like B-ALL cases ( 13 ). In a study, IKZF1 deletions were mostly enriched in the adult Ph+ B-ALL group than in the Ph− B-ALL group (65.9% vs. 20.6%, P < 0.01) ( 5 ).…”

“…In adult B-ALL, IKZF1 deletions were detected about 70% of Ph+ B-ALL cases ( 4 , 5 ), around 15%–30% of Ph− B-ALL ( 53 ), and 40% of Ph-like B-ALL cases ( 13 ). In a study, IKZF1 deletions were mostly enriched in the adult Ph+ B-ALL group than in the Ph− B-ALL group (65.9% vs. 20.6%, P < 0.01) ( 5 ). Ribera reported that IKZF1 deletions were more prevalent in Ph+ B-ALL (52%) and correlated with advanced age and high white blood cell count ( 47 , 57 ).…”