Analysis of carcinogenesis based on TCR rearrangement system

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461580
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Takagi Masatoshi 東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (10406267)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: DNA損傷応答 / T細胞受容体

Outline of Final Research Achievements

The ATM deficient mouse exhibits fewer CD4 and CD8 single positive T-cells due to a failure to develop from the CD4+CD8+ double positive phase to the SP phase. Although the occurrence of chromosome 14 translocations involving TCR alpha gene in ATM-deficient lymphomas suggest that these are early events in T-cell development, an thorough analysis focusing on early T-cell development has never been performed. We demonstrate that ATM deficient T cell are perturbed in passing through the beta or gamma/delta selection checkpoint, leading in part to the developmental failure of T-cells. Detailed karyotype analysis employing in vitro thymocyte development system revealed that RAG mediated TCR alpha/delta locus breaks occur and are left unrepaired during the troublesome beta or gamma/delta selection checkpoints. By getting through these selection checkpoints some of the clones with random or non-random chromosomal translocations involving TC Ralpha/delta locus are selected and accumulate.

Free Research Field

小児血液腫瘍学