Universität zu Köln

Rengstl, Benjamin, Newrzela, Sebastian, Heinrich, Tim, Weiser, Christian, Thalheimer, Frederic B., Schmid, Frederike, Warner, Kathrin, Hartmann, Sylvia, Schroeder, Timm ORCID: 0000-0001-9320-0252, Kueppers, Ralf, Rieger, Michael A. and Hansmann, Martin-Leo (2013). Incomplete cytokinesis and re-fusion of small mononucleated Hodgkin cells lead to giant multinucleated Reed-Sternberg cells. Proc. Natl. Acad. Sci. U. S. A., 110 (51). S. 20729 - 20735. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

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

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rengstl, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Newrzela, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinrich, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Weiser, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Thalheimer, Frederic B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmid, Frederike UNSPECIFIED UNSPECIFIED UNSPECIFIED Warner, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Sylvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, Timm UNSPECIFIED orcid.org/0000-0001-9320-0252 UNSPECIFIED Kueppers, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Rieger, Michael A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansmann, Martin-Leo UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-470006
DOI:	10.1073/pnas.1312509110
Journal or Publication Title:	Proc. Natl. Acad. Sci. U. S. A.
Volume:	110
Number:	51
Page Range:	S. 20729 - 20735
Date:	2013
Publisher:	NATL ACAD SCIENCES
Place of Publication:	WASHINGTON
ISSN:	0027-8424
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language KELCH PROTEIN; T-CELLS; B-CELLS; LYMPHOMA; DISEASE; BIOLOGY; EXPRESSION; REPRESENT; L-428; LINES Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47000