[Correlation between point mutation in ABL kinase and clinical outcome of chronic myeloid leukemia patients].

Abstract

OBJECTIVE:

To analyze the association of different types of ABL tyrosine point mutations and imatinib resistance to probe the relation between ABL tyrosine point mutations and the prognosis of patients with chronic myeloid leukemia (CML).

METHODS:

Nested reverse transcriptasepolym erase chain reaction was performed on samples from 70 patients to amplify the ABL kinase domain. Then, the amplified product was purified and sequenced in both direction. The homologous analysis was performed in combination of clinical data.

RESULTS:

The ABL domain point mutations were detected in 32 patients (45.7%) including 16 patients in chronic phase (CP), 6 patients in accelerated phase(AP)and 10 patients in blast phase (BP), which were detected as T315I, E255K, C475Y, Y253H, G321W, G250E, F317L, E258K, F359V, E459K and F311I, respectively. Sokal score with intermediate and high risk and Ph+ chromosome with complex karyotype were important risk factors for ABL domain point mutations. The 5-year overall survival (OS) was not significantly different between the patients with or without ABL domain point mutations (78.1% vs 84.2%, P=0.985), while the 5-year cumulative event-free survival (EFS) of two groups were 34.4% and 68.4% (P=0.034), respectively. The rate of complete cytogenetic response was higher in patients treated with allogenic hematopetic stem cell transplantation (allo-HSCT) compared with patients merely treated with second-generation tyrosine kinase inhibitors or chemotherapeutics (P=0.001).

CONCLUSION:

Patients with ABL domain point mutations had poor efficacy and prognosis compared to those without ABL domain point mutations. Detection of ABL domain point mutations in CML-CP was helpful for the adjustment of therapeutic options and improvement of prognosis. And allo-HSCT was a more effective therapy for patients with advanced phase.

• Authors: Guanlun Gao, Na Xu, Changxin Yin, Xuan Zhou, Yajuan Xiao, Ling Li, Libin Liao, Rui Cao, Dan Xu, Fanyi Meng, Xiaoli Liu
• Journal: Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi (Zhonghua Xue Ye Xue Za Zhi) Vol. 35 Issue 8 Pg. 703-7 (Aug 2014) ISSN: 0253-2727 [Print] China
• PMID: 25152116 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Piperazines
• Pyrimidines
• Imatinib Mesylate
• Proto-Oncogene Proteins c-abl

Topics

• Adolescent
• Adult
• Aged
• Benzamides (therapeutic use)
• Child
• Drug Resistance, Neoplasm
• Female
• Humans
• Imatinib Mesylate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, genetics)
• Male
• Middle Aged
• Piperazines (therapeutic use)
• Point Mutation
• Prognosis
• Proto-Oncogene Proteins c-abl (genetics)
• Pyrimidines (therapeutic use)
• Young Adult