Cover Image

Accumulation of DNA damage and alteration of the DNA damage response in monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia

Accumulation of DNA damage and alteration of the DNA damage response (DDR) are critical features of genetic instability that is presumed to be implicated in the pathogenesis of monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL). Here, we show increased numbers of γH2AX foci...

Full description

Saved in:
Bibliographic Details
Main Authors: Popp, Henning (Author) , Flach, Johanna (Author) , Brendel, Susanne (Author) , Ruppenthal, Sabrina (Author) , Kleiner, Helga (Author) , Seifarth, Wolfgang (Author) , Schneider, Sven (Author) , Schulze, Torsten (Author) , Weiß, Christel (Author) , Wenz, Frederik (Author) , Hofmann, Wolf-Karsten (Author) , Fabarius, Alice (Author)
Format: Article (Journal)
Language:English
Published: 2019
In: Leukemia and lymphoma
Year: 2019, Volume: 60, Issue: 3, Pages: 795-804
ISSN:1029-2403
DOI:10.1080/10428194.2018.1498494
Online Access:Verlag, Volltext: http://dx.doi.org/10.1080/10428194.2018.1498494
Get full text
Author Notes:Henning D. Popp, Johanna Flach, Susanne Brendel, Sabrina Ruppenthal, Helga Kleiner, Wolfgang Seifarth, Sven Schneider, Torsten J. Schulze, Christel Weiss, Frederik Wenz, Wolf-Karsten Hofmann, Alice Fabarius
Description
Summary:Accumulation of DNA damage and alteration of the DNA damage response (DDR) are critical features of genetic instability that is presumed to be implicated in the pathogenesis of monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL). Here, we show increased numbers of γH2AX foci, a marker of DNA double-strand breaks (DSB), in CD19+ cells of CLL patients as compared to CD19+ cells of MBL patients and healthy individuals. Furthermore, numerous γH2AX/53BP1 foci in CLL cells suggest activation of error-prone non-homologous end-joining repair mechanisms. Signatures of DDR proteins further indicate alterations of the DDR in CLL in contrast to a largely regular activation in MBL and healthy controls. In summary, our results provide evidence for the stepwise accumulation of DNA damage in the progression of MBL towards CLL and suggest increased DNA damage, error-prone DNA repair and altered DDR signaling to be critical mechanisms of clonal evolution in MBL and CLL.
Item Description:Published online: 31 October 2018
Gesehen am 13.06.2019
Physical Description:Online Resource
ISSN:1029-2403
DOI:10.1080/10428194.2018.1498494

Similar Items