Dataset Information

Evolution of TP53 abnormalities during CLL disease course is associated with telomere length changes.

ABSTRACT:

Background

Telomeres are protective structures at chromosome ends which shorten gradually with increasing age. In chronic lymphocytic leukemia (CLL), short telomeres have been associated with unfavorable disease outcome, but the link between clonal evolution and telomere shortening remains unresolved.

Methods

We investigated relative telomere length (RTL) in a well-characterized cohort of 198 CLL patients by qPCR and focused in detail on a subgroup 26 patients who underwent clonal evolution of TP53 mutations (evolTP53). In the evolTP53 subgroup we explored factors influencing clonal evolution and corresponding changes in telomere length through measurements of telomerase expression, lymphocyte doubling time, and BCR signaling activity.

Results

At baseline, RTL of the evolTP53 patients was scattered across the entire RTL spectrum observed in our CLL cohort. RTL changed in the follow-up samples of 16/26 (62%) evolTP53 cases, inclining to reach intermediate RTL values, i.e., longer telomeres shortened compared to baseline while shorter ones prolonged. For the first time we show that TP53 clonal shifts are linked to RTL change, including unexpected RTL prolongation. We further investigated parameters associated with RTL changes. Unstable telomeres were significantly more frequent among younger patients (P = 0.032). Shorter telomeres were associated with decreased activity of the B-cell receptor signaling components p-ERK1/2, p-ZAP-70/SYK, and p-NFκB (P = 0.04, P = 0.01, and P = 0.02, respectively).

Conclusions

Our study revealed that changes of telomere length reflect evolution in leukemic subclone proportion, and are associated with specific clinico-biological features of the explored cohort.

SUBMITTER: Olbertova H

PROVIDER: S-EPMC8812042 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Evolution of TP53 abnormalities during CLL disease course is associated with telomere length changes.

Olbertova Helena H Plevova Karla K Pavlova Sarka S Malcikova Jitka J Kotaskova Jana J Stranska Kamila K Spunarova Michaela M Trbusek Martin M Navrkalova Veronika V Dvorackova Barbara B Tom Nikola N Pal Karol K Jarosova Marie M Brychtova Yvona Y Panovska Anna A Doubek Michael M Pospisilova Sarka S

BMC cancer 20220203 1

<h4>Background</h4>Telomeres are protective structures at chromosome ends which shorten gradually with increasing age. In chronic lymphocytic leukemia (CLL), short telomeres have been associated with unfavorable disease outcome, but the link between clonal evolution and telomere shortening remains unresolved.<h4>Methods</h4>We investigated relative telomere length (RTL) in a well-characterized cohort of 198 CLL patients by qPCR and focused in detail on a subgroup 26 patients who underwent clonal ...[more]

PMID: 35114947

Similar Datasets

Project description:BackgroundThe effects of stress on ill health have become evident in recent years. Under acute stress situations, a cascade of physiological events helps the body mount an appropriate adaptive response. However, under chronic stress situations, this physiological response may lead to wear and tear on the body that accelerates the decline in physiological functioning and increases the risk of chronic conditions. Recent evidence for social stress experienced during childhood suggests serious consequences many years later, even later life. Telomere length, a marker of cell aging, may provide a link between chronic social stress and age-associated physical and mental decline and risk of chronic conditions. This study examines whether chronic social stress is associated with telomere length throughout the life course.Methods/designWe will perform a systematic review of the literature on the relationship between chronic social stress, for example, due to violence, extreme poverty, or caregiving of people with disabling conditions (exposure), and telomere length (outcome) by searching electronic databases in MEDLINE (PubMed interface), EMBASE (OVID interface), Cochrane Central (OVID interface) and gray literature from their start date onwards. We will limit the search to studies performed on human populations. Two reviewers will conduct standardized screening, eligibility assessment, data abstraction, and scientific quality assessment. All study designs investigating the association between chronic social stress and telomere length in healthy or diseased adults and children will be eligible for inclusion in the review. We will extract individual demographic and socioeconomic characteristics, research setting, method of measuring telomere length, reported outcome, and determinants of interest. Studies will also be stratified by 1) age into 3 groups: childhood (0 to 18 years), adulthood (19 to 64 years) and late life (65+); 2) cell type; 3) study design; and 4) telomere length assessment method. Where feasible, study results will be combined through meta-analyses to obtain a pooled measure of associations. Results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement.DiscussionThis systematic review will provide knowledge on the existing evidence for chronic social stress and its association with telomere lengths throughout the life course.

Dataset Information

Evolution of TP53 abnormalities during CLL disease course is associated with telomere length changes.

Background

Methods

Results

Conclusions

Publications

Evolution of TP53 abnormalities during CLL disease course is associated with telomere length changes.

Similar Datasets

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