title: Detection of BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia on imatinib.
abstract: BCR-ABL tyrosine kinase domain mutations are the most important factor contributing to imatinib-resistance in patients with chronic myeloid leukemia. We used a semi-nested reverse transcriptase-polymerase chain reaction followed by bidirectional sequencing to detect mutations in a cohort of 110 chronic myeloid leukemia patients. In total, 34 mutations in 19 distinct codons were identified in 32 patients, of which D276N and E279A were novel. The most commonly mutated region was drug-binding site (29%) followed by P-loop region (26%) and most patients bearing them were in accelerated phase and blastic phase. This report expands the spectrum of BCR-ABL mutations and stresses the use of mutation testing in imatinib-resistant patients for continuation of treatment procedure.
authors.affiliation: Tehran University of Medical Sciences, 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: Zeinab
authors.initials: Z
authors.lastname: Saffari
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Nadali
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Ostadali
authors.forename: Habibeh
authors.initials: H
authors.lastname: Ghadimi
authors.forename: Kamran
authors.initials: K
authors.lastname: Alimoghaddam
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Ghavamzade
authors.forename: Shahrbano
authors.initials: S
authors.lastname: Rostami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D002648:Child; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary; D011743:Pyrimidines / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl