Reed-Sternberg cells form by abscission failure in the presence of functional Aurora B kinase.
Large multinucleated Reed-Sternberg cells (RS) and large mononucleated Hodgkin cells (H) are traditionally considered to be the neoplastic population in classical Hodgkin lymphoma, (cHL) and postulated to promote the disease. However, the contribution of these larger cells to the progression of cHL remains debatable. We used established cHL cell lines and cHL cellular fractions composed of small mononucleated cells only or enriched in large RS/H cells to investigate RS/H cell origin and to characterize the cells which they derive from. We confirm that the small mononucleated cells give rise to RS/H cells, and we show that the latter proliferate significantly more slowly than the small cells. By using live-cell imaging, we demonstrate that binucleated RS cells are generated by failure of abscission when a few small cells attempt to divide. Finally, our results reveal that the small mononucleated cells are chromosomally unstable, but this is unlikely to be related to a malfunctioning chromosomal passenger protein complex. We propose that the small mononucleated cells, rather than the RS/H cells, are the main drivers of cHL.
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Ana
A
Xavier de Carvalho
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Cell Division Unit, Department of Experimental Biology, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, Porto, Portugal.
Helder
H
Maiato
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
André F
AF
Maia
The Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, University of California San Francsicso, San Francisco, United States of America.
Susana A
SA
Ribeiro
Instituto de Patologia e Imunologia Molecular da Universidade do Porto, IPATIMUP, Porto, Portugal.
Patrícia
P
Pontes
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Wendy
W
Bickmore
Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Mayfield Road, Edinburgh, United Kingdom.
William C
WC
Earnshaw
Instituto de Patologia e Imunologia Molecular da Universidade do Porto, IPATIMUP, Porto, Portugal.
Clara
C
Sambade
D064107:Aurora Kinase B / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D006689:Hodgkin Disease / Q000473:pathology; D006801:Humans; D016539:Reed-Sternberg Cells / Q000201:enzymology* / Q000473:pathology*
D002868:Chromosomal Proteins, Non-Histone; D064107:Aurora Kinase B