3D nuclear organization of telomeres in the Hodgkin cell lines U-HO1 and U-HO1-PTPN1: PTPN1 expression prevents the formation of very short telomeres including "t-stumps"

BMC Cell Biology

Research Article

Hans Knecht¹  Bruno Lemieux¹  Peter Möller²  Silke Brüderlein²  Zelda Lichtensztejn³  Sabine Mai³  Daniel Lichtensztejn³  Silke Wegener⁴ 

[1] Division d'Hématologie, CHUS, Université de Sherbrooke, SherbrookeQuébec, Canada;Institute of Pathology, University of Ulm, Ulm, Germany;Manitoba Institute of Cellular Biology, University of Manitoba, Winnipeg, Manitoba, Canada;St. Elisabeth Krankenhaus, Köln, Germany;

关键词: Telomere Length;    Short Telomere;    Nuclear Volume;    Telomeric Repeat Amplification Protocol;    Nuclear Organization;   

DOI  :  10.1186/1471-2121-11-99

 received in 2010-05-31, accepted in 2010-12-14,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundIn cancer cells the three-dimensional (3D) telomere organization of interphase nuclei into a telomeric disk is heavily distorted and aggregates are found. In Hodgkin's lymphoma quantitative FISH (3D Q-FISH) reveals a major impact of nuclear telomere dynamics during the transition form mononuclear Hodgkin (H) to diagnostic multinuclear Reed-Sternberg (RS) cells. In vitro and in vivo formation of RS-cells is associated with the increase of very short telomeres including "t-stumps", telomere loss, telomeric aggregate formation and the generation of "ghost nuclei".ResultsHere we analyze the 3D telomere dynamics by Q-FISH in the novel Hodgkin cell line U-HO1 and its non-receptor protein-tyrosine phosphatase N1 (PTPN1) stable transfectant U-HO1-PTPN1, derived from a primary refractory Hodgkin's lymphoma. Both cell lines show equally high telomerase activity but U-HO1-PTPN differs from U-HO1 by a three times longer doubling time, low STAT5A expression, accumulation of RS-cells (p < 0.0001) and a fourfold increased number of apoptotic cells.As expected, multinuclear U-HO1-RS-cells and multinuclear U-HO1-PTPN1-RS-cells differ from their mononuclear H-precursors by their nuclear volume (p < 0.0001), the number of telomeres (p < 0.0001) and the increase in telomere aggregates (p < 0.003). Surprisingly, U-HO1-RS cells differ from U-HO1-PTPN1-RS-cells by a highly significant increase of very short telomeres including "t-stumps" (p < 0.0001).ConclusionAbundant RS-cells without additional very short telomeres including "t-stumps", high rate of apoptosis, but low STAT5A expression, are hallmarks of the U-HO1-PTPN1 cell line. These characteristics are independent of telomerase activity. Thus, PTPN1 induced dephosphorylation of STAT5 with consecutive lack of Akt/PKB activation and cellular arrest in G2, promoting induction of apoptosis, appears as a possible pathogenetic mechanism deserving further experimental investigation.

【 授权许可】

CC BY   
© Knecht et al; licensee BioMed Central Ltd. 2010