AUTHOR=Feng Jing , Guo Ye , Yang Wenyu , Zou Yao , Zhang Li , Chen Yumei , Zhang Yingchi , Zhu Xiaofan , Chen Xiaojuan 

TITLE=Childhood Acute B-Lineage Lymphoblastic Leukemia With CDKN2A/B Deletion Is a Distinct Entity With Adverse Genetic Features and Poor Clinical Outcomes

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.878098

DOI=10.3389/fonc.2022.878098

ISSN=2234-943X

ABSTRACT=<p>To further emphasize the clinical–genetic features and prognosis of <italic>CDKN2A/B</italic> deletions in childhood acute lymphoblastic leukemia (ALL), we retrospectively analyzed 819 consecutive B-ALL patients treated with the Chinese Children’s Cancer Group ALL-2015 (CCCG-ALL-2015) protocol, and fluorescence <italic>in situ</italic> hybridization (FISH) analysis on <italic>CDKN2A/B</italic> deletion was available for 599 patients. The prevalence of <italic>CDKN2A/B</italic> gene deletions was 20.2% (121/599) of B-ALL. <italic>CDKN2A/B</italic> deletions were significantly associated with older age, higher leukocyte counts, a higher percentage of hepatosplenomegaly, and a higher frequency of <italic>BCR-ABL</italic> (<italic>p</italic> &lt; 0.05). Those patients achieved similar minimal residual disease (MRD) clearance and complete remission compared to patients without <italic>CDKN2A/B</italic> deletion. The <italic>CDKN2A/B</italic> deletions were correlated with inferior outcomes, including a 3-year event-free survival (EFS) rate (69.8 ± 4.6 vs. 89.2 ± 1.6%, <italic>p</italic> = 0.000) and a 3-year overall survival (OS) rate (89.4% ± 2.9% vs. 94.7% ± 1.1%, <italic>p</italic> = 0.037). In multivariable analysis, <italic>CDKN2A/B</italic> deletion was still an independent prognostic factor for EFS in total cohorts (<italic>p</italic> &lt; 0.05). We also detected a multiplicative interaction between <italic>CDKN2A/B</italic> deletions and TP53 deletion on dismal prognosis (<italic>p</italic>-interaction &lt; 0.05). In conclusion, <italic>CDKN2A/B</italic> deletion is associated with distinct characteristics and serves as a poor prognostic factor in pediatric ALL, especially in TP53 deletion carriers.</p>