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CD30 induces Reed-Sternberg cell-like morphology and chromosomal instability in classic Hodgkin lymphoma cell lines |
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| Authors: | Mariko Watanabe Hiromi Hatsuse Kazuaki Nagao Makoto Nakashima Kaoru Uchimaru Makoto Otsu Koji Miyazaki Ryouichi Horie |
| Affiliation: | 1. Division of Hematology, Department of Laboratory Sciences, School of Allied Health Sciences, Kitasato University, Sagamihara, Japan Department of Molecular Cell Therapy, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan;2. Department of Molecular Genetics, School of Medicine, Kitasato University, Sagamihara, Japan;3. Laboratory of Tumor Cell Biology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan;4. Division of Hematology, Department of Laboratory Sciences, School of Allied Health Sciences, Kitasato University, Sagamihara, Japan;5. Department of Molecular Cell Therapy, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan Department of Transfusion and Cell Transplantation, School of Medicine, Kitasato University, Sagamihara, Japan |
| Abstract: | Classic Hodgkin lymphoma (cHL) is characterized by multinucleated cells called Reed-Sternberg (RS) cells and genetic complexity. Although CD30 also characterizes cHL cells, its biological roles are not fully understood. In this report, we examined the link between CD30 and these characteristics of cHL cells. CD30 stimulation increased multinucleated cells resembling RS cells. We found chromatin bridges, a cause of mitotic errors, among the nuclei of multinucleated cells. CD30 stimulation induced DNA double-strand breaks (DSBs) and chromosomal imbalances. RNA sequencing showed significant changes in the gene expression by CD30 stimulation. We found that CD30 stimulation increased intracellular reactive oxygen species (ROS), which induced DSBs and multinucleated cells with chromatin bridges. The PI3K pathway was responsible for CD30-mediated generation of multinucleated cells by ROS. These results suggest that CD30 involves generation of RS cell-like multinucleated cells and chromosomal instability through induction of DSBs by ROS, which subsequently induces chromatin bridges and mitotic error. The results link CD30 not only to the morphological features of cHL cells, but also to the genetic complexity, both of which are characteristic of cHL cells. |
| Keywords: | CD30 chromosomal instability classic Hodgkin lymphoma reactive oxygen species Reed-Sternberg cell |