velikost textu

Výsledky projektu Význam alterace buněčného metabolizmu při vzniku a progresi akutní lymfoblastické leukémie

Výsledky

▼▲Typ výsledku ▼▲Autor celku ▼▲Název celku
(Celkem 4 zázn.)
Katerina Hlozkova, Ivana Hermanova, Lucie Safrhansova, Natividad Alquezar-Artieda, Daniela Kuzilkova, Adela Vavrova, Kristyna Sperkova, Marketa Zaliova, Jan Stary, Jan Trka and Julia Starkova. PTEN/PI3K/Akt pathway alters sensitivity of T-cell acute lymphoblastic leukemia to l-asparaginase. Scientific Reports, 2022, sv. 12, s. 4343–4353. ISSN 2045-2322. IF 4.996. [Článek v časopise]
Childhood T-cell acute lymphoblastic leukemia (T-ALL) still remains a therapeutic challenge due to relapses which are resistant to further treatment. L-asparaginase (ASNase) is a key therapy component in pediatric T-ALL and lower sensitivity of leukemia cells to this drug negatively influences overall treatment efficacy and outcome. PTEN protein deletion and/or activation of the PI3K/Akt signaling pathway leading to altered cell growth and metabolism are emerging as a common feature in T-ALL. We herein investigated the relationship amongst PTEN deletion, ASNase sensitivity and glucose metabolism in T-ALL cells. First, we found significant differences in the sensitivity to ASNase amongst T-ALL cell lines. While cell lines more sensitive to ASNase were PTEN wild type (WT) and had no detectable level of phosphorylated Akt (P-Akt), cell lines less sensitive to ASNase were PTEN-null with high P-Akt levels. Pharmacological inhibition of Akt in the PTEN-null cells rendered them more sensitive to ASNase and lowered their glycolytic function which then resembled PTEN WT cells. In primary T-ALL cells, although P-Akt level was not dependent exclusively on PTEN expression, their sensitivity to ASNase could also be increased by pharmacological inhibition of Akt. In summary, we highlight a promising therapeutic option for T-ALL patients with aberrant PTEN/PI3K/Akt signaling.
Natividad Alquezar Artieda, Poster presentation at ASH meeting 2022. [Jiný výsledek]
Natividad Alquezar Artieda, Covid positive certificate, which shows why I could not attend the conference in Lisbon [Jiný výsledek]
Natividad Alquezar Artieda, Poster Presentation at the Cancer Metabolism Conference in Bilbao [Jiný výsledek]