title: Clinical and proteomic characterization of acute myeloid leukemia with mutated RAS.
abstract: BACKGROUND
  Activating mutations in RAS are frequently present in patients with acute myeloid leukemia (AML), but their overall prognostic impact is not clear.
  
  
  METHODS
  A retrospective analysis was performed to establish the clinical characteristics of patients with RAS-mutated (RAS(mut) ) AML, to analyze their outcome by therapy, and to describe the proteomic profile of RAS(mut) compared with wild-type RAS (RAS(WT) ) AML.
  
  
  RESULTS
  Of 609 patients with newly diagnosed AML, 11% had RAS(mut) . Compared with RAS(WT) , patients with RAS(mut) AML were younger (median age, 54 years vs 63 years; P = .001), had a higher white blood cell count (16K mm(-3) vs 4K mm(-3) ; P < 0.001) and bone marrow blast percentage (56% vs 42%; P = .01) at diagnosis, and were less likely to have an antecedent hematologic disorder (36% vs 50%; P = .03). The inv(16) karyotype was overrepresented in patients with RAS(mut) and the -5 and/or -7 karyotype was underrepresented. RAS mutations were found to have no prognostic impact on overall survival or disease-free survival overall or within cytogenetic subgroups. There was a suggestion that patients with RAS(mut) benefited from cytarabine (AraC)-based therapy. Proteomic analysis revealed simultaneous upregulation of the RAS-Raf-MAP kinase and phosphoinositide 3-kinase (PI3K) signaling pathways in patients with RAS(mut) .
  
  
  CONCLUSIONS
  RAS mutations in AML may delineate a subset of patients who benefit from AraC-based therapy and who may be amenable to treatment with inhibitors of RAS and PI3K signaling pathways.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. tkadia@mdanderson.org
authors.forename: Tapan M
authors.initials: TM
authors.lastname: Kadia
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Steven
authors.initials: S
authors.lastname: Kornblau
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Emil J
authors.initials: EJ
authors.lastname: Freireich
authors.forename: Raja
authors.initials: R
authors.lastname: Luthra
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D011905:Genes, ras; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D012074:Remission Induction; D012189:Retrospective Studies; D015398:Signal Transduction; D055815:Young Adult; D018631:ras Proteins / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D003561:Cytarabine; D018631:ras Proteins