J 2022

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

OLBERTOVÁ, Helena, Karla PLEVOVÁ, Šárka PAVLOVÁ, Jitka MALCIKOVA, Jana KOTAŠKOVÁ et. al.

Basic information

Original name

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

Authors

OLBERTOVÁ, Helena (203 Czech Republic, belonging to the institution), Karla PLEVOVÁ (203 Czech Republic, belonging to the institution), Šárka PAVLOVÁ (203 Czech Republic, belonging to the institution), Jitka MALCIKOVA, Jana KOTAŠKOVÁ (203 Czech Republic, belonging to the institution), Kamila STRÁNSKÁ (203 Czech Republic, belonging to the institution), Michaela ŠPUNAROVÁ (203 Czech Republic, belonging to the institution), Martin TRBUŠEK (203 Czech Republic, belonging to the institution), Veronika NAVRKALOVÁ (203 Czech Republic, belonging to the institution), Barbara DVOŘÁČKOVÁ (203 Czech Republic, belonging to the institution), Nikola TOM (203 Czech Republic, belonging to the institution), Karol PÁL (703 Slovakia, belonging to the institution), Marie JAROŠOVÁ (203 Czech Republic, belonging to the institution), Yvona BRYCHTOVÁ (203 Czech Republic, belonging to the institution), Anna PANOVSKÁ (203 Czech Republic, belonging to the institution), Michael DOUBEK (203 Czech Republic, belonging to the institution) and Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

BMC Cancer, London, BMC, 2022, 1471-2407

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.800

RIV identification code

RIV/00216224:14110/22:00127828

Organization unit

Faculty of Medicine

DOI

UT WoS

000750833300002

Keywords in English

Chronic Lymphocytic Leukemia; Telomere; TP53; Clonal evolution; BCR signaling

Tags

Tags

International impact, Reviewed
Změněno: 17/10/2024 13:32, Ing. Monika Szurmanová, Ph.D.

Abstract

V originále

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.

Links

EF18_046/0015515, research and development project
Name: Modernizace a rozšíření přístrojového vybavení Národního centra lékařské genomiky
GA19-11299S, research and development project
Name: Úloha transpozibilních elementů u hematologických malignit
Investor: Czech Science Foundation
GA19-15737S, research and development project
Name: Alternativní mechanismy deregulace p53 dráhy u chronické lymfocytární leukémie
Investor: Czech Science Foundation, Alternative mechanisms of deregulation of the p53 pathway in chronic lymphocytic leukemia
LM2018133, research and development project
Name: Český národní uzel Evropské infrastruktury pro translační medicínu (Acronym: EATRIS-ERIC-CZ)
Investor: Ministry of Education, Youth and Sports of the CR
MUNI/A/1330/2021, interní kód MU
Name: Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit IX (Acronym: VýDiTeHeMa IX)
Investor: Masaryk University
NU21-08-00237, research and development project
Name: Pokročilé sekvenační metody pro analýzu strukturních přestaveb nádorového genomu
Investor: Ministry of Health of the CR, Advanced sequencing methods for deciphering structural variants in cancer genome, Subprogram 1 - standard
NV19-03-00091, research and development project
Name: Komplexní prognostický a prediktivní panel pro pacienty s chronickou lymfocytární leukémií: nástroj sekvenování nové generace vhodný pro klinickou praxi i studium genetického pozadí průběhu choroby
Investor: Ministry of Health of the CR
90133, large research infrastructures
Name: EATRIS-CZ III