Evolution of TP53 abnormalities during CLL disease course is associated with telomere length changes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F22%3A00076102" target="_blank" >RIV/65269705:_____/22:00076102 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/22:00127828
Result on the web
<a href="https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-09221-z" target="_blank" >https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-09221-z</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1186/s12885-022-09221-z" target="_blank" >10.1186/s12885-022-09221-z</a>
Alternative languages
Result language
angličtina
Original language name
Evolution of TP53 abnormalities during CLL disease course is associated with telomere length changes
Original language description
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-NF kappa B (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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
BMC Cancer
ISSN
1471-2407
e-ISSN
1471-2407
Volume of the periodical
22
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
137
UT code for WoS article
000750833300002
EID of the result in the Scopus database
2-s2.0-85124060442