title: Lack of noncanonical RAS mutations in cytogenetically normal acute myeloid leukemia.
abstract: Transforming mutations in RAS genes are commonly found in human malignancies, including myeloid leukemias. To investigate the incidence, spectrum, and distribution of activating K- and N-RAS mutations in cytogenetically normal acute myeloid leukemia (CN-AML) patients, 204 CN-AML patients were screened. Activating K- and N-RAS mutations were detected in 3 of 204 (1.5 %) and 22 of 204 (10.8 %) CN-AML samples, respectively. RAS mutated patients presented with a lower percentage of bone marrow blasts (65 vs 80 %, P = 0.022). RAS mutations tended to occur with nucleophosmin-1 (NPM1) mutations (P = 0.079), and all three samples containing K-RAS mutations had concomitant NPM1 mutations. There was no significant overlap between K-RAS mutations and N-RAS, FLT3, CEBPA, IDH1/2, WT1 or MLL mutations. RAS mutation status did not impact relapse-free or overall survival of CN-AML patients. In contrast to reports of noncanonical RAS mutations in other cancers, including some leukemia subtypes, we only observed K- and N-RAS mutations in codons 12, 13, or 61 in CN-AML samples. Our findings suggest that while K-RAS mutations are infrequent in CN-AML, activating K-RAS mutations may cooperate with mutated NPM1 to induce leukemia.
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Christoph W M
authors.initials: CW
authors.lastname: Reuter
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Fredrick O
authors.initials: FO
authors.lastname: Onono
authors.forename: Tania
authors.initials: T
authors.lastname: Bunke
authors.forename: Frederik
authors.initials: F
authors.lastname: Damm
authors.forename: Felicitas
authors.initials: F
authors.lastname: Thol
authors.forename: Katharina
authors.initials: K
authors.lastname: Wagner
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morgan
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D001853:Bone Marrow / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D011905:Genes, ras; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin