Pathogenesis of APOBEC3B in childhood leukemia

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10027
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Shimane University
• Principal Investigator: TAKETANI TAKESHI 島根大学, 学術研究院医学・看護学系, 教授 (30359880)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: APOBEC3B

Outline of Final Research Achievements

We examined whether APOBEC3B as a viral defense mechanism contributes to carcinogenesis in childhood leukemia. The frequency of APOBEC3B gene expression in pediatric leukemia samples was low, but C→T mutations were found in 50% of cases, regardless of APOBEC3B gene expression. In addition, cord blood-derived CD34-positive cells into which the shRNA of the IKAROS gene and the PAX5 gene and the TEL-AML1 fusion gene were introduced, respectively, and part of the APOBEC3B gene simultaneously expressed showed cloned proliferation. The clone was found to have reduced differentiation ability, enhanced self-renewal ability and reduced apoptosis. These results suggest that the APOBEC3B gene may contribute to leukemic transformation of pediatric preleukemic clones.

Free Research Field

小児科

Academic Significance and Societal Importance of the Research Achievements

成人の発がんの機序として、紫外線や放射線、抗がん剤、喫煙などの外因子が知られているが、小児がんにおいては、外因子に暴露される機会が成人に比べて極めて少ない。今回、ウイルス防御の１つであるAPOBEC3Bが小児白血病の発症に寄与している可能性を示したことから、感冒などのウイルス感染の予防が小児がん発症の予防になる可能性を示した。