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Accumulation of DNA damage and alteration of the DNA damage response in monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia.
Popp, Henning D; Flach, Johanna; Brendel, Susanne; Ruppenthal, Sabrina; Kleiner, Helga; Seifarth, Wolfgang; Schneider, Sven; Schulze, Torsten J; Weiss, Christel; Wenz, Frederik; Hofmann, Wolf-Karsten; Fabarius, Alice.
Afiliación
  • Popp HD; a Department of Hematology and Oncology , Heidelberg University , Mannheim , Germany.
  • Flach J; a Department of Hematology and Oncology , Heidelberg University , Mannheim , Germany.
  • Brendel S; a Department of Hematology and Oncology , Heidelberg University , Mannheim , Germany.
  • Ruppenthal S; a Department of Hematology and Oncology , Heidelberg University , Mannheim , Germany.
  • Kleiner H; a Department of Hematology and Oncology , Heidelberg University , Mannheim , Germany.
  • Seifarth W; a Department of Hematology and Oncology , Heidelberg University , Mannheim , Germany.
  • Schneider S; b Institute for Clinical Chemistry , Heidelberg University , Mannheim , Germany.
  • Schulze TJ; c Institute of Transfusion Medicine and Immunology , Heidelberg University, German Red-Cross Blood Service Baden-Württemberg - Hessen , Mannheim , Germany.
  • Weiss C; d Department of Medical Statistics and Biomathematics , Heidelberg University , Mannheim , Germany.
  • Wenz F; e Department of Radiation Oncology , Heidelberg University , Mannheim , Germany.
  • Hofmann WK; a Department of Hematology and Oncology , Heidelberg University , Mannheim , Germany.
  • Fabarius A; a Department of Hematology and Oncology , Heidelberg University , Mannheim , Germany.
Leuk Lymphoma ; 60(3): 795-804, 2019 03.
Article en En | MEDLINE | ID: mdl-30376743
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Daño del ADN / Leucemia Linfocítica Crónica de Células B / Evolución Clonal / Linfocitosis Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Leuk Lymphoma Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2019 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Daño del ADN / Leucemia Linfocítica Crónica de Células B / Evolución Clonal / Linfocitosis Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Leuk Lymphoma Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2019 Tipo del documento: Article País de afiliación: Alemania