Patients with Philadelphia-positive leukemia with Y253H or F359V mutation have a high risk of developing new mutations in the setting of dasatinib resistance. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Jiang, Qian; Qin, Ya-Zhen; Lai, Yue-Yun; Jiang, Hao; Wang, Jing; Huang, Xiao-Jun
• Is Part Of: Leukemia & lymphoma. Volume 56:Issue 7(2015:Jul.)
• Page Start: 2075
• Page End: 2081
• Publication Date: 2015-07
• Subjects: Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2014.982639
• Languages: English
• ISSNs: 1042-8194

Abstract

<abstract> <title>Abstract</title> <p>The treatment outcome and development of new mutations in patients with imatinib- and/or nilotinib-failure Philadelphia chromosome positive (Ph+) leukemia with highly nilotinib-resistant mutations (Y253H, E255K/V and F359V/C) were assessed on dasatinib therapy. A total of 111 patients with Ph+ leukemia were grouped into three cohorts by baseline BCR–ABL kinase domain mutation status: no mutation (<italic>n</italic> = 44), non-nilotinib-resistant mutations (<italic>n</italic> = 26) or nilotinib-resistant mutations (<italic>n</italic> = 41). The frequencies of hematological, cytogenetic and molecular responses and clinical resistance to dasatinib were similar among the three cohorts during dasatinib therapy. In dasatinib-resistant patients, new mutations were most frequently observed in the cohort with nilotinib-resistant mutations (<italic>p</italic> = 0.001). Multivariate analysis revealed that advanced disease and harboring Y253H or F359V mutation before dasatinib were independent predictors of developing new mutations. We conclude that patients with Ph+ leukemia with Y253H or F359V mutation have a high likelihood of developing new mutations in the setting of dasatinib resistance.</p> </abstract>