Multidisciplinary insight into clonal expansion of HTLV-1–infected cells in adult T-cell leukemia via modeling by deterministic finite automata coupled with high-throughput sequencing

摘要

BackgroundClonal expansion of leukemic cells leads to onset of adult T-cell leukemia (ATL), an aggressive lymphoid malignancy with a very poor prognosis. Infection with human T-cell leukemia virus type-1 (HTLV-1) is the direct cause of ATL onset, and integration of HTLV-1 into the human genome is essential for clonal expansion of leukemic cells. Therefore, monitoring clonal expansion of HTLV-1–infected cells via isolation of integration sites assists in analyzing infected individuals from early infection to the final stage of ATL development. However, because of the complex nature of clonal expansion, the underlying mechanisms have yet to be clarified. Combining computational/mathematical modeling with experimental and clinical data of integration site–based clonality analysis derived from next generation sequencing technologies provides an appropriate strategy to achieve a better understanding of ATL development.