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%2F12%3A00057983" target="_blank" >RIV/00216224:14330/12:00057983 - isvavai.cz</a>

Výsledek na webu

<a href="http://abstracts.hematologylibrary.org/content/vol120/issue21/" target="_blank" >http://abstracts.hematologylibrary.org/content/vol120/issue21/</a>

DOI - Digital Object Identifier

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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

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hemopoietic stem cells. The constitutively active tyrosine kinase BCR-ABL causes defects in the proliferation and differentiation of blood cells. CML is currently treated with tyrosine kinase specific inhibitors (TKIs), such as imatinib, nilotinib, and dasatinib. Transient, potent BCR-ABL inhibition with TKIs was demonstrated to commit CML cells to apoptosis irreversibly (Shah et al., 2008; Snead et al., 2009; Hiwase et al. 2009).This mechanism would explain the clinical efficacy of once-daily dasatinib treatment, despite the rapid clearance of the drug from the plasma. The restoration of BCR-ABL activity after TKI washout was demonstrated using phosphorylated CRKL (p-CRKL) protein as a surrogate marker. Our in vitro data challenges this model.

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

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hemopoietic stem cells. The constitutively active tyrosine kinase BCR-ABL causes defects in the proliferation and differentiation of blood cells. CML is currently treated with tyrosine kinase specific inhibitors (TKIs), such as imatinib, nilotinib, and dasatinib. Transient, potent BCR-ABL inhibition with TKIs was demonstrated to commit CML cells to apoptosis irreversibly (Shah et al., 2008; Snead et al., 2009; Hiwase et al. 2009).This mechanism would explain the clinical efficacy of once-daily dasatinib treatment, despite the rapid clearance of the drug from the plasma. The restoration of BCR-ABL activity after TKI washout was demonstrated using phosphorylated CRKL (p-CRKL) protein as a surrogate marker. Our in vitro data challenges this model.

Druh

O - Ostatní výsledky

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

2012

Kód důvěrnosti údajů

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