Apoptosis in chronic myeloid leukemia cells transiently treated with imatinib or dasatinib is caused by residual BCR-ABL kinase inhibition.

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14330%2F13%3A00066079" target="_blank" >RIV/00216224:14330/13:00066079 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.ncbi.nlm.nih.gov/pubmed/23420553" target="_blank" >http://www.ncbi.nlm.nih.gov/pubmed/23420553</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ajh.23419" target="_blank" >10.1002/ajh.23419</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Apoptosis in chronic myeloid leukemia cells transiently treated with imatinib or dasatinib is caused by residual BCR-ABL kinase inhibition.

Popis výsledku v původním jazyce

Transient, potent BCR-ABL inhibition with tyrosine kinase inhibitors (TKIs) was recently demonstrated to be sufficient to commit chronic myeloid leukemia (CML) cells to apoptosis irreversibly. This mechanism explains the clinical efficacy of once-daily dasatinib treatment, despite the rapid clearance of the drug from the plasma. However, our in vitro data suggest that apoptosis induction after transient TKI treatment, observed in the BCR-ABL-positive cell lines K562, KYO-1, and LAMA-84 and progenitor cells from chronic phase CML patients, is instead caused by a residual kinase inhibition that persists in the cells as a consequence of intracellular drug retention. High intracellular concentrations of imatinib and dasatinib residues were measured in transiently treated cells. Furthermore, the apoptosis induced by residual imatinib or dasatinib from transient treatment could be rescued by washing out the intracellularly retained drugs.

Název v anglickém jazyce

Apoptosis in chronic myeloid leukemia cells transiently treated with imatinib or dasatinib is caused by residual BCR-ABL kinase inhibition.

Popis výsledku anglicky

Transient, potent BCR-ABL inhibition with tyrosine kinase inhibitors (TKIs) was recently demonstrated to be sufficient to commit chronic myeloid leukemia (CML) cells to apoptosis irreversibly. This mechanism explains the clinical efficacy of once-daily dasatinib treatment, despite the rapid clearance of the drug from the plasma. However, our in vitro data suggest that apoptosis induction after transient TKI treatment, observed in the BCR-ABL-positive cell lines K562, KYO-1, and LAMA-84 and progenitor cells from chronic phase CML patients, is instead caused by a residual kinase inhibition that persists in the cells as a consequence of intracellular drug retention. High intracellular concentrations of imatinib and dasatinib residues were measured in transiently treated cells. Furthermore, the apoptosis induced by residual imatinib or dasatinib from transient treatment could be rescued by washing out the intracellularly retained drugs.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

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Projekt

<a href="/cs/project/GBP302%2F12%2FG157" target="_blank" >GBP302/12/G157: Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2013

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

American Journal of Hematology

ISSN

0361-8609

e-ISSN

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Svazek periodika

88

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

385-393

Kód UT WoS článku

000318043500423

EID výsledku v databázi Scopus

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