title: Frequent coexistence of RAS mutations in RUNX1-mutated acute myeloid leukemia in Arab Asian children.
abstract: BACKGROUND
  RUNX1 mutation plays an important role in adult leukemic transformation. However, its contribution to the development of childhood leukemia remains unclear. In the present study, we analyzed point mutations of RUNX1 gene in children and adolescents with acute myeloid leukemia (AML) from Iraq and Jordan.
  
  
  METHODS
  Bone marrow and/or peripheral blood samples were collected from 178 patients of Arab Asian ethnicity (aged ≤17 years) newly diagnosed with AML: 145 samples from Iraq and 33 samples from Jordan. Direct DNA sequencing was performed on six genes including RUNX1 gene (exons 3-8).
  
  
  RESULTS
  RUNX1 point mutations were identified in 10 (5.6%) of 178 patients. One patient possessed biallelic mutations of RUNX1 gene. C-terminal area was the predominant site of RUNX1 mutations (eight in C-terminal and two in N-terminal). Patients with RUNX1 mutations were significantly older than those with wild-type of the gene. Additionally, AML M0 subtype was more frequently found in patients with RUNX1 mutations. Both RUNX1 mutations and RAS mutations were identified in 4 of 10 children. Three patients with RUNX1 mutation had FLT3-ITD. On the other hand, 36 (21.4%) and 25 (14.9%) of 168 patients with wild-type of the gene had a RAS mutation and FLT3-ITD, respectively. Eight of 10 patients with RUNX1 mutations died of hematological relapse.
  
  
  CONCLUSIONS
  The incidence of RUNX1 mutations in Arab Asian children and adolescents with AML was 5.6%. Further studies are required to clarify whether RAS mutations contribute to the development of pediatric AML associated with RUNX1 mutations.
authors: Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors: Lika'a Fasih Y
authors: LF
authors: Al-Kzayer
authors: Kazuo
authors: K
authors: Sakashita
authors: Mazin Faisal
authors: MF
authors: Al-Jadiry
authors: Salma Abbas
authors: SA
authors: Al-Hadad
authors: Le T N
authors: le TN
authors: Uyen
authors: Tingting
authors: T
authors: Liu
authors: Kazuyuki
authors: K
authors: Matsuda
authors: Jaafar M H
authors: JM
authors: Abdulkadhim
authors: Tariq Abadi
authors: TA
authors: Al-Shujairi
authors: Zead Ismael I K
authors: ZI
authors: Matti
authors: Janan Ghalib
authors: JG
authors: Hasan
authors: Hussam M Salih
authors: HM
authors: Al-Abdullah
authors: Toshi
authors: T
authors: Inoshita
authors: Minoru
authors: M
authors: Kamata
authors: Maher A
authors: MA
authors: Sughayer
authors: Faris F
authors: FF
authors: Madanat
authors: Kenichi
authors: K
authors: Koike
mesh_terms: D000293:Adolescent; D018912:Arabs; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000208:ethnology / Q000235:genetics*; D008297:Male; D009154:Mutation; D017354:Point Mutation
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human
keywords: AML; C-terminal/N-terminal; FTA; MDS; RAS; RUNX1/AML1