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2018 Fiscal Year Final Research Report

Molecular analysis of pediatric MDS/AML

Research Project

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Project/Area Number 15K09653
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionOkayama University

Principal Investigator

Shimada Akira  岡山大学, 大学病院, 准教授 (70391836)

Project Period (FY) 2015-04-01 – 2019-03-31
Keywords骨髄異形成症候群 / 急性骨髄性白血病 / がん抑制遺伝子 / メチル化
Outline of Final Research Achievements

Epigenetic status of the promotor region on tumor suppressor gened (TSGs) in pediatric myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) are still remains unknown. We analyzed the aberrant methylation of promotor region of 25 TSGs in pediatric 7 low grade MDS, 4 advanced MDS and 22 AML patients by FAB classification by MS-MLPA method. Total 12/22(54.5%) patients had more than one methylated TSGs (number of methylated TSGs was 0-5 in each patient, median 1). More than 20% of patients had methylated TSGs including CDKN2B, CADM1, CDH13 and ESR1. Especially, all (4/4) t(8;21) patients had CDH13 methylation, 3/4 (75%) patients with inv(16) had ESR1 methylation and normal karyotype did not. Complete remission samples, and low grade MDS samples were not methylated. All advanced MDS patients had 1 or 2 methylated TSGs. In this study, many genes related to epigenetic modification such as ASXL1, TET2 and EZH2 were not mutated. Aberrant methylation was started in advanced MDS.

Free Research Field

小児血液腫瘍学

Academic Significance and Societal Importance of the Research Achievements

成人と比較して、小児の骨髄異形成症候群(MDS)/急性骨髄性白血病(AML)でもがん抑制遺伝子のメチル化がみられたことは、今後小児でも抗メチル化薬の応用が期待できる。また成人とは異なりepigenetic modifier遺伝子の変異はみられなかったことは重要と考えられる。

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Published: 2020-03-30  

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