ALL-257 Detection of Deletion in the IKZF1 Gene and the NOTCH1 Signaling Pathway in Patients With T-Cell Acute Lymphoblastic Leukemia: Data of the RALL Study Group

Abstract

Mutation in the NOTCH1 is the most frequent event in patients with T-acute lymphoblastic leukemia (ALL). This mutation is associated with a favorable prognosis. Deletion of the IKZF1 gene, occurring in patients with T-ALL in about 10% of cases, is a prognostically unfavorable anomaly. To evaluate the survival of patients with T-ALL depending on the immunophenotype, as well as to analyze the frequency of occurrence of anomalies in the NOTCH1 and IKZF1 genes. The analysis included 91 patients with T-ALL/LBL receiving therapy according to the ALL-2016 protocol. The immunophenotype was determined by flow cytofluorimetry. Anomalies in the IKZF1 and NOTCH1 were investigated by fragment analysis according to Caye A, et al and Campregher PV, et al in 25 and 29 patients, respectively. From December 2016 to June 2021, 91 patients with T-ALL were included in the ALL-2016 protocol (64 men and 27 women, median 32 years: 6-TIV, 11-ETP-ALL, 32-TI/II, 42-TIII). 3-year overall survival in the ETP group was 28%, TI/II-50%, TIII-73% and TIV-83%. Molecular anomalies in NOTCH1 were analyzed by fragment analysis in 29 patients (1-undifferentiated variant, 8-ETP-ALL, 9-TIII, 10-TIII, 1-TIV), in IKZF1 genes in 25 patients (1-undifferentiated variant, 5-ETP-ALL, 8-TIII, 10-TIII, 1-TIV). None of the patients had deletions in the IKZF1. Anomalies in the NOTCH1 were detected in 19 (65.5%) patients (4-ETP-ALL, 7-TII, 7-TIII, 1-TIV). At the same time, 15 of them (51%) had NOTCH1 deletions, 4 (14%) had insertions. 5 patients without abnormalities in the NOTCH1 (50%) died as a result of a resistant or relapse, 5 patients are alive in remission. In the group of patients with an anomaly in the NOTCH1, 3 patients (16%) died, the remaining 16 patients (84%) are alive in remission. Overall survival was 84% in the group with anomalies versus 50% in the group without anomalies (p=0.05). Anomalies in the NOTCH1 are the most common in patients with T-ALL. This mutation is associated with a more favorable prognosis.