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Frequent coexistence of RAS mutations in RUNX1 ‐mutated acute myeloid leukemia in Arab Asian children
Author(s) -
AlKzayer Lika'a Fasih Y.,
Sakashita Kazuo,
AlJadiry Mazin Faisal,
AlHadad Salma Abbas,
Uyen Le T.N.,
Liu Tingting,
Matsuda Kazuyuki,
Abdulkadhim Jaafar M.H.,
AlShujairi Tariq Abadi,
Matti Zead Ismael I.K.,
Hasan Janan Ghalib,
AlAbdullah Hussam M. Salih,
Inoshita Toshi,
Kamata Minoru,
Sughayer Maher A.,
Madanat Faris F.,
Koike Kenichi
Publication year - 2014
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.25151
Subject(s) - runx1 , medicine , myeloid leukemia , leukemia , point mutation , exon , mutation , gene mutation , gene , myeloid , cancer research , genetics , biology , transcription factor
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. Procedure 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. Conclusion 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. Pediatr Blood Cancer 2014;61:1980–1985. © 2014 Wiley Periodicals, Inc.