Journal
CANCER SCIENCE
Volume 114, Issue 4, Pages 1556-1568Publisher
WILEY
DOI: 10.1111/cas.15706
Keywords
CD30 signaling; chromosomal instability; DNA double-strand breaks; lymphomagenesis; reactive oxygen species
Categories
Ask authors/readers for more resources
Adult T-cell leukemia/lymphoma (ATL) develops through the accumulation of gene mutations and chromosome aberrations. CD30 signaling induces chromosomal instability and clonal expansion in ATL cells. CD30 expression is correlated with genomic instability, suggesting its role as an oncogenic factor in ATL progression with clonal evolution.
Adult T-cell leukemia/lymphoma (ATL) develops via stepwise accumulation of gene mutations and chromosome aberrations. However, the molecular mechanisms underlying this tumorigenic process 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 human T-cell leukemia virus type 1 (HTLV-1)-infected cells that display polylobulation. Here, we demonstrated that CD30 signaling induced chromosomal instability with clonal expansion through DNA double-strand breaks (DSBs) via an increase of intracellular reactive oxygen species. CD30(+)ATL cells were composed of subclones with additional genomic aberrations compared with CD30(-)ATL cells in ATL patients. Furthermore, we found an accumulation of copy number loss of DSB repair-related genes as the disease progressed. Taken together, CD30 expression on ATL cells appears to be correlated with genomic instability, suggesting that CD30 signaling is one of the oncogenic factors of ATL progression with clonal evolution. This study provides new insight into the biological roles of CD30 signaling and could improve our understanding of tumorigenic processes of HTLV-1-infected cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available