Telomere shortening, TP53 mutations and deletions in chronic lymphocytic leukemia result in increased chromosomal instability and breakpoint clustering in heterochromatic regions.
Ann Hematol
; 96(9): 1493-1500, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28691153
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.
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MEDLINE
Assunto principal:
Sequência de Bases
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Heterocromatina
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Leucemia Linfocítica Crônica de Células B
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Proteína Supressora de Tumor p53
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Deleção de Sequência
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Instabilidade Cromossômica
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Homeostase do Telômero
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article