[Characteristics of NOTCH1 mutation in adult T-cell acute lymphoblastic leukemia]

This study was aimed to investigate the characteristics and clinical significance of NOTCH1 mutation in adult T-cell acute lymphoblastic leukemia (T-ALL). Exon 26/N-terminal region of the heterodimerization domain (HD-N) , exon 27/ C-terminal region of the heterodimerization domain (HD-C) , exon 28 and exon 34/ proline-glutamic acid-serine-threonine (PEST) domain of the NOTCH1 gene were amplified, cloned and sequenced in 42 adult patients with T-ALL to identify the frequency, position and type of NOTCH1 mutation, their correlations with laboratorial and clinical parameters, as well as their relevant prognostic significance. The results showed that the frequency of NOTCH1 mutation in this cohort of adult patients was 66.7% (28/42); A total of 45 types of NOTCH1 mutations were identified in present study, most of them were in HD-N (48.9%, 22/45) and PEST (40.0%, 18/45) domains. Mutation in amino acid 1575 (L1575P) was the top one type of mutation in HD-N (25.0%, 7/28), and amino acid 2443 was the most common mutation position in PEST domain (14.3%, 4/28). In newly diagnosed patients, white blood cell (WBC) >10×10(9)/L and blasts in bone marrow > 50% were predominant in patients with NOTCH1 mutation (91.7% vs 54.5%, P = 0.021 and 95.8% vs 57.1%, P = 0.006 respectively). Immunophenotyping analysis indicated that patients with CD10 positive were more in NOTCH1 mutation group than wild-type group (51.9% vs 0%, P = 0.006), whereas patients with CD15 and CD11b positive were less in NOTCH1 mutation group (5.3% vs 42.9%, P = 0.047 and 0% vs 57.1%, P = 0.002 respectively). It is concluded that NOTCH1 mutation in adult T-ALL has different characteristics and clinical significance from pediatric patients, and the difference between Chinese patients and patients in Western countries is also indicated.