Molecular analyses and the development of targeting therapy of pediatric acute myeloid leukemia using next generation sequencer

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390268
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Gunma Institute of Public Health and Environmental Sciences
• Principal Investigator: HAYASHI YASUHIDE 群馬県衛生環境研究所, 研究企画係, 研究員 (30238133)
• Co-Investigator(Kenkyū-buntansha): ICHIKAWA Hitoshi 独立行政法人国立がん研究センター, その他部局等, その他 (30201924) ; OHKI Kentaro 群馬県衛生環境研究所, 研究企画係, 研究員 (50400966) ; PARK Myoung-ja 群馬県衛生環境研究所, 研究企画係, 研究員 (50450375) ; SOTOMATSU Manabu 群馬県衛生環境研究所, 研究企画係, 研究員 (70251113)
• Co-Investigator(Renkei-kenkyūsha): OGAWA Seishi 国立大学法人京都大学大学院医学研究科, 腫瘍生物学, 教授 (50292900)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 次世代シーケンサー / コヒーシン / 急性骨髄性白血病

Outline of Final Research Achievements

Whole-exome resequencing of 19 cases with acute myeloid leukemia (AML) was analyzed with a mean coverage of approximately x100. A total of 80 somatic mutations or 4.2 mutations per sample was identified. The mean number of somatic mutations in pediatric AML might be fewer than in adult AML. Many mutations identified in this study involved previously reported targets in AML. On the other hand, several genes including BCOR, BCORL1, ASXL2, MLL2,3, SMC3 and RAD21 were newly identified. Furthermore, we examined mutations of these genes in pediatric 192 AML patients by gene targeting. In total, 32 mutations were identified in 31 of these specimens. The mutually exclusive pattern of the mutations in these BCOR, BCORL1 and cohesin components genes was confirmed in this study, suggesting a common impact of these mutations on the pathogenesis of pediatric AML. Our results indicated that a subset of pediatric AML represents a discrete entity different from the adult AML.

Free Research Field

小児血液・腫瘍学