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Annals of Hematology

, Volume 96, Issue 9, pp 1493–1500 | Cite as

Telomere shortening, TP53 mutations and deletions in chronic lymphocytic leukemia result in increased chromosomal instability and breakpoint clustering in heterochromatic regions

  • Kathrin Thomay
  • Caroline Fedder
  • Winfried Hofmann
  • Hans Kreipe
  • Michael Stadler
  • Jan Titgemeyer
  • Ingo Zander
  • Brigitte Schlegelberger
  • Gudrun GöhringEmail author
Original Article

Abstract

Complex karyotypes are associated with a poor prognosis in chronic lymphocytic leukemia (CLL). Using mFISH, iFISH, and T/C-FISH, we thoroughly characterized 59 CLL patients regarding parameters known to be involved in chromosomal instability: status of the genes ATM and TP53 and telomere length. Interestingly, a deletion of the ATM locus in 11q, independent of the cytogenetic context, was associated with significantly diminished risk (p<0.05) of carrying a mutation in TP53. In patients with loss or mutation of TP53, chromosomal breakage occurred more frequently (p<0.01) in (near-) heterochromatic regions. Median telomere length in patients with complex karyotypes was significantly shorter than that of healthy controls and shorter than in all other cytogenetic cohorts. Furthermore, the median telomere length of patients carrying a TP53 mutation was significantly shorter than without mutation. We conclude that telomere shortening in combination with loss of TP53 induces increased chromosomal instability with preferential involvement of (near-) heterochromatic regions.

Keywords

Chromosomal instability Structurally complex karyotype Telomeres TP53 ATM Chronic lymphocytic leukemia CLL Breakpoint clustering 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

For this type of study formal consent is not required.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Funding

This study was funded by the Cluster of Excellence REBIRTH (from Regenerative Biology to Reconstructive Therapy, EXC 6273).

Supplementary material

277_2017_3055_MOESM1_ESM.pdf (220 kb)
ESM 1 (PDF 220 kb).
277_2017_3055_MOESM2_ESM.pdf (185 kb)
ESM 2 (PDF 184 kb).
277_2017_3055_MOESM3_ESM.pdf (253 kb)
ESM 3 (PDF 253 kb).

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Kathrin Thomay
    • 1
  • Caroline Fedder
    • 1
  • Winfried Hofmann
    • 1
  • Hans Kreipe
    • 2
  • Michael Stadler
    • 3
  • Jan Titgemeyer
    • 4
  • Ingo Zander
    • 5
  • Brigitte Schlegelberger
    • 1
  • Gudrun Göhring
    • 1
    Email author
  1. 1.Department of Human GeneticsHannover Medical SchoolHannoverGermany
  2. 2.Institute of PathologyHannover Medical SchoolHannoverGermany
  3. 3.Department of Hematology, Hemostasis, Oncology and Stem Cell TransplantationHannover Medical SchoolHannoverGermany
  4. 4.Onkologische Praxis CelleCelleGermany
  5. 5.Onkologie am RaschplatzHannoverGermany

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