Resistance to targeted therapies in chronic lymphocytic
leukemia: Current status and perspectives for clinical and
diagnostic practice

J 2025

Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice

BLOMBERY, Piers; Thomas CHATZIKONSTANTINOU; Marina GEROUSI; Richard ROSENQUIST; Gianluca GAIDANO et. al.

Základní údaje

Originální název

Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice

Autoři

Vydání

Leukemia, LONDON, SPRINGERNATURE, 2025, 0887-6924

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 12.800 v roce 2023

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1038/s41375-025-02662-y

UT WoS

001514279700001

EID Scopus

999

Štítky

14110212, 14110323

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 7. 7. 2025 08:27, Mgr. Tereza Miškechová

Anotace

V originále

The integration of BTK and BCL2 inhibitors into the treatment of patients with chronic lymphocytic leukemia (CLL) represents a paradigm shift and has led to significant improvements in clinical outcomes, including prolonged survival and enhanced quality of life. However, despite the efficacy of these agents, resistance to targeted therapy remains a major challenge, ultimately resulting in treatment failure and disease progression for a significant proportion of patients. Related to this, diagnostic testing for genetic variants associated with resistance, such as mutations in BTK, PLCG2 and BCL2, may become an increasingly common part of clinical routine practice. Addressing the need for placing the current knowledge in context, here we summarize the evidence from clinical studies and examine the underlying biology of both genetic and non-genetic resistance. Furthermore, we outline methodological approaches for the detection of gene alterations associated with targeted therapy resistance, discuss how to interpret these findings and highlight interpretation challenges. Finally, we offer insights into the clinical relevance of identifying genetic resistance to inform personalized treatment strategies and improve patient outcomes.

Citovat

BLOMBERY, Piers; Thomas CHATZIKONSTANTINOU; Marina GEROUSI; Richard ROSENQUIST; Gianluca GAIDANO; Šárka POSPÍŠILOVÁ; Andrew W ROBERTS; Richard W BIRKINSHAW; Davide ROSSI; Lydia SCARFO; John F SEYMOUR; Stephan STILGENBAUER; Adrian WIESTNER; Jennifer A WOYACH; Jennifer R BROWN; Paolo GHIA a Kostas STAMATOPOULOS. Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice. Leukemia. LONDON: SPRINGERNATURE, 2025, 12 s. ISSN 0887-6924. Dostupné z: https://dx.doi.org/10.1038/s41375-025-02662-y.

@article{2507518,
   author = {Blombery, Piers and Chatzikonstantinou, Thomas and Gerousi, Marina and Rosenquist, Richard and Gaidano, Gianluca and Pospíšilová, Šárka and Roberts, Andrew W and Birkinshaw, Richard W and Rossi, Davide and Scarfo, Lydia and Seymour, John F and Stilgenbauer, Stephan and Wiestner, Adrian and Woyach, Jennifer A and Brown, Jennifer R and Ghia, Paolo and Stamatopoulos, Kostas},
   article_location = {LONDON},
   doi = {http://dx.doi.org/10.1038/s41375-025-02662-y},
   language = {eng},
   issn = {0887-6924},
   journal = {Leukemia},
   title = {Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice},
   url = {https://www.nature.com/articles/s41375-025-02662-y},
   year = {2025}
}

TY  - JOUR
ID  - 2507518
AU  - Blombery, Piers - Chatzikonstantinou, Thomas - Gerousi, Marina - Rosenquist, Richard - Gaidano, Gianluca - Pospíšilová, Šárka - Roberts, Andrew W - Birkinshaw, Richard W - Rossi, Davide - Scarfo, Lydia - Seymour, John F - Stilgenbauer, Stephan - Wiestner, Adrian - Woyach, Jennifer A - Brown, Jennifer R - Ghia, Paolo - Stamatopoulos, Kostas
PY  - 2025
TI  - Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice
JF  - Leukemia
PB  - SPRINGERNATURE
SN  - 08876924
UR  - https://www.nature.com/articles/s41375-025-02662-y
N2  - The integration of BTK and BCL2 inhibitors into the treatment of patients with chronic lymphocytic leukemia (CLL) represents a paradigm shift and has led to significant improvements in clinical outcomes, including prolonged survival and enhanced quality of life. However, despite the efficacy of these agents, resistance to targeted therapy remains a major challenge, ultimately resulting in treatment failure and disease progression for a significant proportion of patients. Related to this, diagnostic testing for genetic variants associated with resistance, such as mutations in BTK, PLCG2 and BCL2, may become an increasingly common part of clinical routine practice. Addressing the need for placing the current knowledge in context, here we summarize the evidence from clinical studies and examine the underlying biology of both genetic and non-genetic resistance. Furthermore, we outline methodological approaches for the detection of gene alterations associated with targeted therapy resistance, discuss how to interpret these findings and highlight interpretation challenges. Finally, we offer insights into the clinical relevance of identifying genetic resistance to inform personalized treatment strategies and improve patient outcomes.
ER  -

BLOMBERY, Piers; Thomas CHATZIKONSTANTINOU; Marina GEROUSI; Richard ROSENQUIST; Gianluca GAIDANO; Šárka POSPÍŠILOVÁ; Andrew W ROBERTS; Richard W BIRKINSHAW; Davide ROSSI; Lydia SCARFO; John F SEYMOUR; Stephan STILGENBAUER; Adrian WIESTNER; Jennifer A WOYACH; Jennifer R BROWN; Paolo GHIA a Kostas STAMATOPOULOS. Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice. \textit{Leukemia}. LONDON: SPRINGERNATURE, 2025, 12 s. ISSN~0887-6924. Dostupné z: https://dx.doi.org/10.1038/s41375-025-02662-y.

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