Cover Image

DNA damage and DNA damage response in chronic myeloid leukemia

DNA damage and alterations in the DNA damage response (DDR) are critical sources of genetic instability that might be involved in BCR-ABL1 kinase-mediated blastic transformation of chronic myeloid leukemia (CML). Here, increased DNA damage is detected by γH2AX foci analysis in peripheral b...

Full description

Saved in:
Bibliographic Details
Main Authors: Popp, Henning (Author) , Samra, Vanessa (Author) , Naumann, Nicole (Author) , Flach, Johanna (Author) , Brendel, Susanne (Author) , Kleiner, Helga (Author) , Weiß, Christel (Author) , Seifarth, Wolfgang (Author) , Saußele, Susanne (Author) , Hofmann, Wolf-Karsten (Author) , Fabarius, Alice (Author)
Format: Article (Journal)
Language:English
Published: 11 February 2020
In: International journal of molecular sciences
Year: 2020, Volume: 21, Issue: 4
ISSN:1422-0067
DOI:10.3390/ijms21041177
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms21041177
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/21/4/1177
Get full text
Author Notes:Henning D. Popp, Vanessa Kohl, Nicole Naumann, Johanna Flach, Susanne Brendel, Helga Kleiner, Christel Weiss, Wolfgang Seifarth, Susanne Saussele, Wolf-Karsten Hofmann and Alice Fabarius
Description
Summary:DNA damage and alterations in the DNA damage response (DDR) are critical sources of genetic instability that might be involved in BCR-ABL1 kinase-mediated blastic transformation of chronic myeloid leukemia (CML). Here, increased DNA damage is detected by γH2AX foci analysis in peripheral blood mononuclear cells (PBMCs) of de novo untreated chronic phase (CP)-CML patients (n = 5; 2.5 γH2AX foci per PBMC ± 0.5) and blast phase (BP)-CML patients (n = 3; 4.4 γH2AX foci per PBMC ± 0.7) as well as CP-CML patients with loss of major molecular response (MMR) (n = 5; 1.8 γH2AX foci per PBMC ± 0.4) when compared to DNA damage in PBMC of healthy donors (n = 8; 1.0 γH2AX foci per PBMC ± 0.1) and CP-CML patients in deep molecular response or MMR (n = 26; 1.0 γH2AX foci per PBMC ± 0.1). Progressive activation of erroneous non-homologous end joining (NHEJ) repair mechanisms during blastic transformation in CML is indicated by abundant co-localization of γH2AX/53BP1 foci, while a decline of the DDR is suggested by defective expression of (p-)ATM and (p-)CHK2. In summary, our data provide evidence for the accumulation of DNA damage in the course of CML and suggest ongoing DNA damage, erroneous NHEJ repair mechanisms, and alterations in the DDR as critical mediators of blastic transformation in CML.
Item Description:Gesehen am 16.04.2020
Physical Description:Online Resource
ISSN:1422-0067
DOI:10.3390/ijms21041177

Similar Items