title: Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after therapy with tyrosine kinase inhibitors.
abstract: Mutations in codon 317 after treatment with imatinib and dasatinib have been reported. We reviewed patients with chronic myeloid leukemia and mutations after tyrosine kinase inhibitor (TKI) therapy. F317L was detected in 20, including 12/99 (12%) with mutation after imatinib failure, and 8/16 (50%) after dasatinib (P = .001). Median follow-up from mutation detection was 25 months. At the time of F317L, 8 patients were in chronic phase (CP), 6 in accelerated phase, and 6 in blast phase. There was no difference in characteristics between patients with or without F317L mutations, or with no mutations. A complete cytogenetic response was achieved in 3 of 6 patients treated with nilotinib, 2 of 2 with imatinib, and 0 of 3 with dasatinib. Survival of patients with F317L was similar to those with other mutations (P = .45). Patients in CP had better outcome, with a 2-year survival of 75%. F317L mutation is resistant to dasatinib but sensitive to other TKIs. The prognosis is dependent mostly on the disease stage.
authors.affiliation: Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Neeli
authors.initials: N
authors.lastname: Reddy
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Jan
authors.initials: J
authors.lastname: Burger
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D002648:Child; D000069439:Dasatinib; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate; D013844:Thiazoles / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib