Identification of molecular target of high risk pediatric AML by comprehensive genetic analysis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K20951
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics; Hematology
• Research Institution: Yokohama City University (2017-2018); Gunma University (2016)
• Principal Investigator: SHIBA NORIO 横浜市立大学, 医学部, 講師 (50600615)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 小児 / 急性骨髄性白血病 / DNAメチル化 / 抑制性ポリコーム

Outline of Final Research Achievements

Lots of gene alterations were identified and used for risk stratification by next generation sequencing. We investigated genome-wide DNA methylation patterns in pediatric patients with AML, and enabled to predict the prognosis particular in patients with FLT3-ITD which was known as adverse prognostic marker.
Surprisingly, when we examined the relation between high PRDM16 expression and PRDM16 methylation sites, most of hypermethylatedion sites were gene body, and located at important regions which were the targets of repressed polycomb in leukemic blast cells.

Free Research Field

血液腫瘍

Academic Significance and Societal Importance of the Research Achievements

小児、成人を問わず、急性骨髄性白血病は予後不良疾患であるが、今回の解析結果は、今後、不必要な造血幹細胞移植を回避したり、新たな分子標的薬の導入やメチル化阻害剤の適応症例の抽出などを可能とする可能性がある。その結果、治療成績の向上、移植治療関連死亡や治療関連の後遺症、合併症を減らすことができ、QOL向上に繋がることが期待される。