Exp Mol Med.  2005 Oct;37(5):507-511.

Detection of single nucleotide insertion of BCR/ABL region in imatinib-resistant human myelogenous leukemia SR-1 cells

Affiliations
  • 1Department of Internal Medicine, Dong-A University College of Medicine, Busan 602-715, Korea.
  • 2Department of Laboratory Medicine, Dong-A University College of Medicine, Busan 602-715, Korea.
  • 3Department of Pathology, Dong-A University College of Medicine, Busan 602-715, Korea.
  • 4Department of Biochemistry, Dong-A University College of Medicine, Busan 602-715, Korea. jipark@dau.ac.kr

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.

Keyword

drug resistance, neoplasm; frameshift mutation; fusion proteins, bcr-abl; imatinib; leukemia, myeloid, chronic

MeSH Terms

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
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