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@proceedings{1079654,
author = {Šimara, Pavel and Stejskal, Stanislav and Krontorád Koutná, Irena and Potěšil, David and Tesařová, Lenka and Potěšilová, Michaela and Zdráhal, Zbyněk and Mayer, Jiří},
booktitle = {54th ASH Annual Meeting and Exposition},
keywords = {Chronic Myeloid Leukemia; Imatinib; Dasatinib},
language = {eng},
title = {Apoptosis in Chronic Myeloid Leukemia Cells Transiently Treated with Imatinib or Dasatinib Is Caused by Residual BCR-ABL Kinase Inhibition},
url = {http://abstracts.hematologylibrary.org/content/vol120/issue21/},
year = {2012}
}
TY - CONF
ID - 1079654
AU - Šimara, Pavel - Stejskal, Stanislav - Krontorád Koutná, Irena - Potěšil, David - Tesařová, Lenka - Potěšilová, Michaela - Zdráhal, Zbyněk - Mayer, Jiří
PY - 2012
TI - Apoptosis in Chronic Myeloid Leukemia Cells Transiently Treated with Imatinib or Dasatinib Is Caused by Residual BCR-ABL Kinase Inhibition
KW - Chronic Myeloid Leukemia
KW - Imatinib
KW - Dasatinib
UR - http://abstracts.hematologylibrary.org/content/vol120/issue21/
L2 - http://abstracts.hematologylibrary.org/content/vol120/issue21/
N2 - 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. We suggest that apoptosis observed in the BCR-ABL-positive cell lines K562, KYO-1, LAMA-84 and progenitor cells from chronic phase CML patients with transient imatinib and dasatinib treatment is instead caused by residual kinase inhibition that persists as a consequence of intracellular drug retention.
ER -
ŠIMARA, Pavel, Stanislav STEJSKAL, Irena KRONTORÁD KOUTNÁ, David POTĚŠIL, Lenka TESAŘOVÁ, Michaela POTĚŠILOVÁ, Zbyněk ZDRÁHAL a Jiří MAYER. Apoptosis in Chronic Myeloid Leukemia Cells Transiently Treated with Imatinib or Dasatinib Is Caused by Residual BCR-ABL Kinase Inhibition. In \textit{54th ASH Annual Meeting and Exposition}. 2012. ISSN~1528-0020.
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