title: Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study.
abstract: Distinct forms of tyrosine kinase domain (TKD), juxtamembrane domain, exon 8, and internal tandem duplication (ITD) mutations of c-KIT, were observed in about 46% of core binding factor leukemia (CBFL) patients. To evaluate their prognostic significance, 67 adult patients with CBFL were analyzed to ascertain the c-KIT mutation status. In acute myeloid leukemia (AML) with t(8;21), the presence of c-KIT TKD mutation at codon 816 (TKD(816)) was associated with a high white blood cell count at diagnosis (median, 29.60 x 10(9)/L) and a higher incidence (33%) of extramedullary leukemia (EML) during the course of the disease. Data also showed that the TKD(816) mutated patients (n = 12) had a significantly higher incidence of relapse and a lower overall survival (OS) at 24 months, compared with the 17 c-KIT unmutated (c-KIT(-)) patients (90% vs 35.3%, P = .002; 25% vs 76.5%, P = .006, respectively). No difference in relapse incidence (P = .126) and OS (P = .474) was observed between the c-KIT mutated other than TKD(816) (n = 7) and the c-KIT(-) patients. These findings indicate that c-KIT TKD(816) mutation has a negative impact on the outcome of AML with t(8;21).
authors.affiliation: Division of Hematology, Ospedale Niguarda, Piazza Ospedale Maggiore 3, 20162-Milano, Italy. roberto.cairoli@ospedaleniguarda.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Cairoli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Beghini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grillo
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Nadali
authors.forename: Francesca
authors.initials: F
authors.lastname: Elice
authors.forename: Carla Barbara
authors.initials: CB
authors.lastname: Ripamonti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Colapietro
authors.forename: Michele
authors.initials: M
authors.lastname: Nichelatti
authors.forename: Laura
authors.initials: L
authors.lastname: Pezzetti
authors.forename: Monia
authors.initials: M
authors.lastname: Lunghi
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuneo
authors.forename: Assunta
authors.initials: A
authors.lastname: Viola
authors.forename: Felicetto
authors.initials: F
authors.lastname: Ferrara
authors.forename: Mario
authors.initials: M
authors.lastname: Lazzarino
authors.forename: Francesco
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pizzolo
authors.forename: Lidia
authors.initials: L
authors.lastname: Larizza
authors.forename: Enrica
authors.initials: E
authors.lastname: Morra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D050660:Core Binding Factors / Q000235:genetics*; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics* / Q000401:mortality; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012189:Retrospective Studies; D014178:Translocation, Genetic
chemical_list: D050660:Core Binding Factors; D019009:Proto-Oncogene Proteins c-kit