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@article{2245079,
author = {Olbertová, Helena and Plevová, Karla and Pavlová, Šárka and Malcikova, Jitka and Kotašková, Jana and Stránská, Kamila and Špunarová, Michaela and Trbušek, Martin and Navrkalová, Veronika and Dvořáčková, Barbara and Tom, Nikola and Pál, Karol and Jarošová, Marie and Brychtová, Yvona and Panovská, Anna and Doubek, Michael and Pospíšilová, Šárka},
article_location = {London},
article_number = {1},
doi = {http://dx.doi.org/10.1186/s12885-022-09221-z},
keywords = {Chronic Lymphocytic Leukemia; Telomere; TP53; Clonal evolution; BCR signaling},
language = {eng},
issn = {1471-2407},
journal = {BMC Cancer},
title = {Evolution of TP53 abnormalities during CLL disease course is associated with telomere length changes},
url = {https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-09221-z},
volume = {22},
year = {2022}
}
TY - JOUR
ID - 2245079
AU - Olbertová, Helena - Plevová, Karla - Pavlová, Šárka - Malcikova, Jitka - Kotašková, Jana - Stránská, Kamila - Špunarová, Michaela - Trbušek, Martin - Navrkalová, Veronika - Dvořáčková, Barbara - Tom, Nikola - Pál, Karol - Jarošová, Marie - Brychtová, Yvona - Panovská, Anna - Doubek, Michael - Pospíšilová, Šárka
PY - 2022
TI - Evolution of TP53 abnormalities during CLL disease course is associated with telomere length changes
JF - BMC Cancer
VL - 22
IS - 1
SP - 1-11
EP - 1-11
PB - BMC
SN - 14712407
KW - Chronic Lymphocytic Leukemia
KW - Telomere
KW - TP53
KW - Clonal evolution
KW - BCR signaling
UR - https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-09221-z
N2 - 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.
ER -
OLBERTOVÁ, Helena, Karla PLEVOVÁ, Šárka PAVLOVÁ, Jitka MALCIKOVA, Jana KOTAŠKOVÁ, Kamila STRÁNSKÁ, Michaela ŠPUNAROVÁ, Martin TRBUŠEK, Veronika NAVRKALOVÁ, Barbara DVOŘÁČKOVÁ, Nikola TOM, Karol PÁL, Marie JAROŠOVÁ, Yvona BRYCHTOVÁ, Anna PANOVSKÁ, Michael DOUBEK and Šárka POSPÍŠILOVÁ. Evolution of TP53 abnormalities during CLL disease course is associated with telomere length changes. \textit{BMC Cancer}. London: BMC, 2022, vol.~22, No~1, p.~1-11. ISSN~1471-2407. Available from: https://dx.doi.org/10.1186/s12885-022-09221-z.
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