Examination of point mutations within the ABL kinase domine region of BCR/ABL in patients with chronic myeloid leukemia who develop imatinib resistance
- VernacularTitle:伊马替尼耐药的慢性粒细胞白血病患者ABL激酶区点突变检测的意义
- Author:
Dong-Guang YANG
;
Ri ZHANG
;
Jian-Nong CEN
;
Zi-Ling ZHU
;
- Publication Type:Journal Article
- Keywords:
Leukemia,myeloid,chronic;
Drug resistenee;
Point mutation
- From:
Chinese Journal of Laboratory Medicine
2003;0(11):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the point mutations within the adenosine triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemia who develop imatinib resistance.Methods We collected a total of 17 bone marrow samples obtained from 11 patients who showed hematology resistance (n = 7)or cytogenetic refractoriness(n = 4).A long semi-nest PCR method was used to amplify the ABL kinase domain of the BCR/ABL allele.After two rounds of PCR reactions,we got a fragment of 863 bases The PCR products were purified and followed by sequencing.Results In total,we find three point mutations presented in all patients tested G250E,E255K and T315I.The mutation rate of hematology resistance is 4/ 7,and 95% confidence interval was 8%-90%,while mutation rate of cytogenetic refractoriness 1/4,95% confidence interval 1%-81%.For those patients whose samples were available,no single mutation were determined before imatinib resistance emerged.Conclusions There is high frequency of point mutations clustered within the adenosine triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemia.It's good for patients to switch to another therapeutic strategy when the mutations are detected.
