title: On the origin of giant cells in Hodgkin lymphoma.
abstract: Multinucleated giant tumor cells are frequently observed in tissue sections of lymphoma patients. In Hodgkin lymphoma (HL), these cells are pathognomonic for the disease and named Reed-Sternberg (RS) cells. Despite the well-described disease-promoting functions of RS cells, their development has remained obscure. We addressed this open question by continuous live cell imaging to observe the generation of RS cells. Single-cell tracking of HL cell lines revealed that RS cells develop from mononucleated progenitors that divide and subsequently re-fuse, before they grow and become multinucleated giant cells. Thus, RS cell generation is neither due to cell fusion of unrelated Hodgkin cells nor to endomitosis, as previously suggested. In the majority of cases, re-fusion of daughter cells was preceded by an incomplete cytokinesis, visualized by a persistent microtubule bridge connecting the cells. This surprising finding describes a novel mechanism for the formation of multinuclear giant cells with potential relevance beyond HL.
authors.affiliation: Dr. Senckenberg Institute of Pathology; Goethe-University of Frankfurt Medical School; Frankfurt am Main, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rengstl
authors.affiliation: LOEWE Center for Cell and Gene Therapy Frankfurt; Department of Hematology/Oncology; Goethe-University of Frankfurt Medical School; Frankfurt am Main, Germany ; German Cancer Consortium (DKTK); Heidelberg, Germany ; German Cancer Research Center (DKFZ); Heidelberg, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rieger
authors.affiliation: Dr. Senckenberg Institute of Pathology; Goethe-University of Frankfurt Medical School; Frankfurt am Main, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Newrzela
keywords: Hodgkin lymphoma; Reed-Sternberg cells; acytokinetic mitosis; cell fusion; endomitosis; giant cells; incomplete cytokinesis; re-fusion; single-cell tracking; time-lapse microscopy