title: RAS mutations are frequent in FAB type M4 and M5 of acute myeloid leukemia, and related to late relapse: a study of the Japanese Childhood AML Cooperative Study Group.
abstract: Mutations in RAS are frequent in acute myeloid leukemia (AML), and are thought to contribute to leukemogenesis in a subset of patients; however, their prognostic significance has not been firmly established. One hundred and fifty-seven pediatric patients with AML were analyzed for NRAS and KRAS mutations around hot spots at codons 12, 13, and 61. Twenty-nine patients (18.5%) had an activating mutation of RAS. We found KRAS mutations to be more frequent than NRAS mutations (18/29, 62.1% of patients with RAS mutation), in contrast to previous reports (18-40%). The frequency of RAS mutation was higher in French-American-British types M4 and M5 than other types (P = 0.02). There were no significant differences in other clinical manifestations or distribution in cytogenetic subgroups, or aberrations of other genes, including KIT mutation, FLT3-ITD, and MLL-PTD, between patients with and without RAS mutations. No significant differences were observed in the 3-year overall survival and disease-free survival; however, the presence of RAS mutation was related to late relapse. The occurrence of clinical events at relatively late period should be monitored for in AML patients with mutations in RAS.
authors.affiliation: Department of Hematology/Oncology, Gunma Children's Medical Center, 779 Shimohakoda, Hokkitsu, Shibukawa, Gunma, 377-8577, Japan.
authors.forename: Hirozumi
authors.initials: H
authors.lastname: Sano
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taki
authors.forename: Chisato
authors.initials: C
authors.lastname: Murata
authors.forename: Myoung-Ja
authors.initials: MJ
authors.lastname: Park
authors.forename: Manabu
authors.initials: M
authors.lastname: Sotomatsu
authors.forename: Ken
authors.initials: K
authors.lastname: Tabuchi
authors.forename: Akio
authors.initials: A
authors.lastname: Tawa
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuchida
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hanada
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tsukimoto
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control*; D008297:Male; D009154:Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012008:Recurrence; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins