a 2023

FOXO1-RICTOR AXIS induces adaptive increase in AKT activity during BCR inhibitor therapy in CLL: Implications for combination therapy.

ONDRIŠOVÁ, Laura; Václav ŠEDA; Giorgia CHIODIN; Kryštof HLAVÁČ; Lenka KOŠŤÁLOVÁ et al.

Basic information

Original name

FOXO1-RICTOR AXIS induces adaptive increase in AKT activity during BCR inhibitor therapy in CLL: Implications for combination therapy.

Authors

ONDRIŠOVÁ, Laura; Václav ŠEDA; Giorgia CHIODIN; Kryštof HLAVÁČ; Lenka KOŠŤÁLOVÁ; Daniel FILIP; Pedro FARIA ZENI; Anna PANOVSKÁ; Karla PLEVOVÁ; Šárka POSPÍŠILOVÁ; Martin ŠIMKOVIČ; Filip VRBACKÝ; Daniel LYSÁK; Stacey M. FERNANDEZ; MS. DAVIDS; Alba MAIQUES-DIAZ; Stella CHARALAMPOPOULOU; Jose I. MARTIN-SUBERO; Jennifer R. BROWN; Michael DOUBEK; Francesco FORCONI; Jiří MAYER and Marek MRÁZ

Edition

EHA 2023 in HemaSphere (2023), 2023

Other information

Language

English

Type of outcome

Konferenční abstrakta

Country of publisher

Germany

Confidentiality degree

is not subject to a state or trade secret

References:

Marked to be transferred to RIV

No

Organization

Středoevropský technologický institut – Repository – Repository

ISSN

Keywords in English

BCR inhibitors; BTK inhibitors; CCL; BCR; FoxO1/Rictor

Links

LX22NPO5102, research and development project. MUNI/A/1224/2022, interní kód Repo. 802644, interní kód Repo.
Changed: 25/3/2024 03:21, RNDr. Daniel Jakubík

Abstract

In the original language

Genetic mechanisms of resistance to BCR inhibitors in CLL have been extensively described. However, it remainsunknown whether non-genetic adaptation mechanisms to BTK inhibitors might exist. We focused on the possible role of the Akt pathway in adapting to BCR inhibitors since, in mouse models, PI3K-Akt activation is the only known factor that rescues the apoptosis induced by BCR deletion in mature B cells. We aim to describe non-genetic mechanisms of adaptation to BCR inhibitor therapy. We performed transcriptome profiling (Illumina) and analyzed samples obtained from CLL patients before and during ibrutinib or idelalisib therapy and performed gene editing in MEC1 cells to reveal the functional role of FoxO1/Rictor.