The oncogenic driving force of CD30 signaling-induced chromosomal instability in adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATL) is characterized by a high frequency of chromosomal aberrations; however, the molecular mechanisms underlying this chromosomal instability are poorly understood. We previously reported the presence of a biological link between the expression of CD30, which serves as a marker for ATL progression, and the actively proliferating fraction of HTLV-1-infected cells that display polylobulation. We demonstrate that CD30 signaling triggers chromosomal instability with clonal expansion in primary CD30-expressing ATL cells and clarifies the molecular mechanisms. Furthermore, we investigate the expression mechanism of CD30, whose gene name is TNFRSF8, using the ChIP-Sequence and Hi-C methods. This study highlights that CD30 signaling is one of the oncogenic factors of ATL progression with clonal evolution and that CD30 is a promising therapeutic target for ATL.