title: Evaluation of T315I mutation frequency in chronic myeloid leukemia patients after imatinib resistance.
abstract: The occurrence of resistance mutations in the Abl kinase domain plays a central role in drug treatment failure in chronic myeloid leukemia (CML) patients. Among them, the T315I mutation at the gatekeeper position affects a common Abl kinase contact residue and confers complete resistance to all known ATP-competitive BCR-ABL inhibitors. In the present study, an allele-specific oligonucleotide reverse transcriptase polymerase chain reaction assay was used to detect T315I mutation in a cohort of 60 imatinib-resistant CML patients. In terms of disease phase, 43 patients (71%) were in late chronic phase, 4 (7%) in accelerated phase, and 13 (22%) in blastic phase. The prevalence of the T315I mutation was found to be 7% (4/60). All four patients with mutation were in advance phases and had previously lost all their responses. The results of the study confirmed that this method is low cost and easy tool to operate for T315I mutation screening and direct sequencing should be performed in positive cases for confirmation.
authors.affiliation: Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Shariati Hospital, Kargar Avenue, Tehran, Iran.
authors.forename: Bahram
authors.initials: B
authors.lastname: Chahardouli
authors.forename: Farhad
authors.initials: F
authors.lastname: Zaker
authors.forename: Seied Asadollah
authors.initials: SA
authors.lastname: Mousavi
authors.forename: Ahmad
authors.initials: A
authors.lastname: Kazemi
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Ostadali
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Nadali
authors.forename: Shahrbano
authors.initials: S
authors.lastname: Rostami
authors.forename: Kamran
authors.initials: K
authors.lastname: Alimoghaddam
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Ghavamzade
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D015415:Biomarkers; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl