Incomplete cytokinesis and re-fusion of small mononucleated Hodgkin cells lead to giant multinucleated Reed–Sternberg cells

摘要: Multinucleated Reed-Sternberg (RS) cells are pathognomonic for classical Hodgkin lymphoma (HL), and their presence is essential diagnosis. How these giant tumor develop controversial, however. It has been postulated that RS arise from mononucleated via endomitosis. Conversely, continuous single-cell tracking of HL cell lines by long-term time-lapse microscopy identified fusion as the main route formation. In contrast to growth-induced formation cells, small mononuclear followed a size increase gives rise cells. Of note, originating same ancestor, termed re-fusion, seen nearly exclusively. majority cases, re-fusion daughter preceded incomplete cytokinesis, demonstrated microtubule bonds among We confirm at level individual tracked have little proliferative capacity, further supporting compartment clone. addition, sister show shared propensity providing evidence early fate commitment. Thus, generation related neither unrelated nor endomitosis, but rather mediated underwent mitosis. This surprising finding supports existence unique mechanism multinuclear may implications beyond HL, given RS-like frequently observed in several other lymphoproliferative diseases well.