Short Telomeres?

Short Telomeres?

Short telomere length is associated with NOTCH1/SF3B1/TP53 aberrations and poor outcome in newly diagnosed chronic lymphocytic leukemia patients according to this Swedish study by Richard Rosenquist and his team...

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Most previous studies on telomere length (TL) in chronic lymphocytic leukemia (CLL) are based on referral cohorts including a high proportion of aggressive cases.

Here, the impact of TL was analyzed in a population-based cohort of newly diagnosed CLL (n=265) and in relation to other prognostic markers. Short telomeres were particularly associated with high-risk genetic markers, such as NOTCH1, SF3B1 or TP53 aberrations, and predicted a short time to treatment (TTT) and overall survival (OS) (both P<0.0001). TL was an independent prognostic factor and subdivided patients with otherwise good-prognostic features (e.g. mutated IGHV genes, favorable cytogenetics) into subgroups with different outcome. Furthermore, in follow-up samples (n=119) taken 5-8 years after diagnosis, TL correlated well with TL at diagnosis and remained unaffected by treatment.

Altogether, these novel data indicate that short TL already at diagnosis is associated with poor outcome in CLL and that TL can be measured at later stages of the disease.

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Abstract...

onlinelibrary.wiley.com/doi...

Telomeres

en.wikipedia.org/wiki/Telomere

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  • Study explains how genetic mutations linked to telomere capping complex contribute to cancers.

    Scientists at The Wistar Institute have unveiled part of the protein complex that protects telomeres-;the ends of our chromosomes. The study, published online in Nature Communications, explains how a group of genetic mutations associated with this protein complex contributes to various cancers.

    Telomeres are the protective structures at the end of chromosomes and are essential for the faithful replication and protection of our genome. Defects in telomere function can lead to genomic instability in cancer, while the gradual shortening of telomeres is associated with the aging of human cells. A key component of the telomere protecting mechanism is a multi-protein complex called shelterin. Shelterin protects chromosome ends from triggering DNA damage response mechanisms; it also regulates telomere maintenance and replication by the enzyme telomerase.

    This new study describes the atomic structure of the protein-protein interaction between two subunits of the shelterin complex, POT1 and TPP1. Several gene mutations have been described as affecting portions of POT1 in familial melanoma, glioma and chronic lymphocytic leukemia. Based on a host of structural, biochemical and cell-based data, the study explains how these mutations may contribute to malignant transformation.

    news-medical.net/news/20170...

    PHILADELPHIA — (April 10, 2017) — Scientists at The Wistar Institute have unveiled part of the protein complex that protects telomeres—the ends of our chromosomes. The study, published online in Nature Communications, explains how a group of genetic mutations associated with this protein complex contributes to various cancers.

    Telomeres are the protective structures at the end of chromosomes and are essential for the faithful replication and protection of our genome. Defects in telomere function can lead to genomic instability in cancer, while the gradual shortening of telomeres is associated with the aging of human cells. A key component of the telomere protecting mechanism is a multi-protein complex called shelterin. Shelterin protects chromosome ends from triggering DNA damage response mechanisms; it also regulates telomere maintenance and replication by the enzyme telomerase.

    wistar.org/news-and-media/p...

    Dick

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