Leukemogenesis and Molecular Characteristics of Tumor Cells

Chapter

Abstract

Adult T-cell leukemia (ATL) develops in carriers of human T-cell leukemia virus (HTLV-1) in adulthood after a long period of clinical latency. Epidemiological data have demonstrated that leukemogenesis is based on a multistep carcinogenesis model involving five or more genetic events. However, detailed genetic and epigenetic events that lead to the transformation of HTLV-1-infected cells have not yet been clarified. This chapter summarizes the current knowledge on the clonal growth of HTLV-1-infected cells, including ATL cells in vivo, gene expression profiles, and genetic and epigenetic events characterized to date. HTLV-1-infected T cells immortalized by HTLV-1 have been shown to result in polyclonal growth in vivo, with over 10,000 clones. ATL cells usually arise from one specific clone; however, occasional concurrent transformation can result in ATL with multiple clones. A multicolor fluorescence-activated cell sorting (FACS) system developed to identify and sort HTLV-1-infected CD4+ T cells enabled the characterization of cellular and genetic/epigenetic changes during malignant transformation in vivo. Next-generation sequencing (NGS) techniques have led to studies that provide a comprehensive landscape of genetic abnormalities in ATL cells. Revelation of the epigenetic landscape of ATL cells, combined with genetic information, provided the basis for understanding abnormalities in the transcriptome of ATL cells. This new set of information advanced our understanding of leukemogenesis and provided the basis for drug development, although mechanisms underlying the progressive accumulation of these abnormalities remain to be clarified.

Keywords

Clonality Epigenome Next-generation sequencing Transcriptome 

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Copyright information

© Springer Japan KK 2017

Authors and Affiliations

  1. 1.Department of Medical Genome Sciences, Graduate School of Frontier SciencesThe University of TokyoTokyoJapan

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