title: Analysis of KRAS and NRAS Gene Mutations in Arab Asian Children With Acute Leukemia: High Frequency of RAS Mutations in Acute Lymphoblastic Leukemia.
abstract: BACKGROUND
  KRAS and NRAS gene mutations are frequently observed in childhood leukemia. The objective of this study was to determine the frequency of RAS mutations and the association between RAS mutations and other genetic aberrations in Arab Asian children with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).
  
  
  METHODS
  Diagnostic samples of 485 patients (<18 years) with acute leukemia from Iraq and Jordan were obtained, using Flinders Technology Associates filter papers. Polymerase chain reaction and direct sequencing were performed in Japan.
  
  
  RESULTS
  RAS mutations were detected in 86/318 (27%) of ALL cases and 35/167 (21%) of AML cases. The frequency of NRAS mutation was similar to that of KRAS mutation in ALL. Two RAS mutations were detected in nine patients. Among 264 Iraqi patients with ALL, RAS mutation was significantly associated with lower initial white blood cell count. Of 57 patients with chimeric transcripts, only two patients with either TEL-AML1 or E2A-PBX1 had KRAS mutation. The frequency of NRAS mutation was four times higher than that of KRAS mutation in AML. FAB-M4 and M5 subsets were associated with RAS mutation. Among 134 Iraqi patients with AML, 18 patients had RAS mutations and other genetic aberrations. In particular, 9 of 25 (36%) with MLL-rearrangement had RAS mutations.
  
  
  CONCLUSIONS
  The prevalence of oncogenic RAS mutations was higher among Arab Asian children than in other countries. RAS mutations in AML were found to coexist with other genetic aberrations, particularly MLL rearrangement.
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Lika'a Fasih Y
authors.initials: LF
authors.lastname: Al-Kzayer
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sakashita
authors.affiliation: Department of Pediatrics, College of Medicine, Baghdad University, Baghdad Medical City, Baghdad, Iraq.|Department of Pediatric Oncology, Children's Welfare Teaching Hospital, Baghdad Medical City, Baghdad, Iraq.
authors.forename: Mazin Faisal
authors.initials: MF
authors.lastname: Al-Jadiry
authors.affiliation: Department of Pediatrics, College of Medicine, Baghdad University, Baghdad Medical City, Baghdad, Iraq.|Department of Pediatric Oncology, Children's Welfare Teaching Hospital, Baghdad Medical City, Baghdad, Iraq.
authors.forename: Salma Abbas
authors.initials: SA
authors.lastname: Al-Hadad
authors.affiliation: Department of Pediatrics, College of Medicine, Baghdad University, Baghdad Medical City, Baghdad, Iraq.|Department of Pediatric Oncology, Children's Welfare Teaching Hospital, Baghdad Medical City, Baghdad, Iraq.
authors.forename: Hasanein Habeeb
authors.initials: HH
authors.lastname: Ghali
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Le T N
authors.initials: le TN
authors.lastname: Uyen
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Nagano, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Department of Pediatric Oncology, Central Teaching Hospital for Children, Baghdad, Iraq.
authors.forename: Jaafar M H
authors.initials: JM
authors.lastname: Abdulkadhim
authors.affiliation: Department of Pediatric Oncology, Central Teaching Hospital for Children, Baghdad, Iraq.
authors.forename: Tariq Abadi
authors.initials: TA
authors.lastname: Al-Shujairi
authors.affiliation: Department of Pediatric Oncology, Central Teaching Hospital for Children, Baghdad, Iraq.
authors.forename: Zead Ismael I K
authors.initials: ZI
authors.lastname: Matti
authors.affiliation: Department of Pathology, King Hussein Cancer Center, Amman, Jordan.
authors.forename: Maher A
authors.initials: MA
authors.lastname: Sughayer
authors.affiliation: Department of Pediatrics, King Hussein Cancer Center, Amman, Jordan.
authors.forename: Rawad
authors.initials: R
authors.lastname: Rihani
authors.affiliation: Department of Pediatrics, King Hussein Cancer Center, Amman, Jordan.
authors.forename: Faris F
authors.initials: FF
authors.lastname: Madanat
authors.affiliation: Japan Iraq Medical Network, Tokyo, Japan.
authors.forename: Toshi
authors.initials: T
authors.lastname: Inoshita
authors.affiliation: Japan Chernobyl Foundation, Matsumoto, Nagano, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Kamata
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koike
mesh_terms: D000293:Adolescent; D018912:Arabs; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007493:Iraq; D007597:Jordan; D015470:Leukemia, Myeloid, Acute / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D059645:Mutation Rate; D051788:Myeloid-Lymphoid Leukemia Protein; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000208:ethnology / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: C497422:KMT2A protein, human; C117307:KRAS protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: ALL; AML; Arab Asian children; FTA; MLL-rearrangement; RAS