Detection of single nucleotide insertion of BCR/ABL region in imatinib-resistant human myelogenous leukemia SR-1 cells.
- Author:
Tae Ho PARK
1
;
Hyuk Chan KWON
;
Hyo Jin KIM
;
Jin Yeong HAN
;
Jin Sook JEONG
;
Hoon HAN
;
Chi Yeon SEO
;
Jong Young KWAK
;
Joo In PARK
Author Information
1. Department of Internal Medicine, Dong-A University College of Medicine, Busan 602-715, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
drug resistance, neoplasm;
frameshift mutation;
fusion proteins, bcr-abl;
imatinib;
leukemia, myeloid, chronic
- MeSH:
Amino Acid Sequence;
Base Sequence;
Cell Line, Tumor;
Drug Resistance, Neoplasm/*genetics;
Fusion Proteins, bcr-abl/chemistry/*genetics;
Humans;
Leukemia, Myeloid/*genetics;
Molecular Sequence Data;
Mutagenesis, Insertional/*genetics;
Nucleotides/genetics;
Piperazines/*pharmacology;
Point Mutation/*genetics;
Pyrimidines/*pharmacology;
Research Support, Non-U.S. Gov't
- From:Experimental & Molecular Medicine
2005;37(5):507-511
- CountryRepublic of Korea
- Language:English
-
Abstract:
Imatinib mesylate is a selective Bcr/Abl kinase inhibitor and an effective anticancer agent for Bcr/Abl-positive chronic myelogenous leukemia. Most patients in chronic phase maintain durable responses; however, many in blast crisis fail to respond, or relapse quickly. Mutations within the BCR/ABL kinase domain are the most commonly identified mechanism associated with relapse. To overcome the imatinib resistance in CML, many investigators have tried to clarify molecular mechanism for imatinib resistance in cells of patients who failed to respond to imatinib. Our aim was to invesitigate underlying mechanism for imatinib resistance in SR-1 cells, which were derived from a CML patient in blast crisis. We detected the new mutation of BCR/ABL, resulting in premature termination and loss of BCR/ABL fusion protein expression, which might be possible mechanism for the resistance to imatinib in SR-1 cells.
