Detailed Information on Publication Record
2012
Apoptosis in Chronic Myeloid Leukemia Cells Transiently Treated with Imatinib or Dasatinib Is Caused by Residual BCR-ABL Kinase Inhibition
ŠIMARA, Pavel, Stanislav STEJSKAL, Irena KRONTORÁD KOUTNÁ, David POTĚŠIL, Lenka TESAŘOVÁ et. al.Basic information
Original name
Apoptosis in Chronic Myeloid Leukemia Cells Transiently Treated with Imatinib or Dasatinib Is Caused by Residual BCR-ABL Kinase Inhibition
Authors
ŠIMARA, Pavel (203 Czech Republic, belonging to the institution), Stanislav STEJSKAL (203 Czech Republic, belonging to the institution), Irena KRONTORÁD KOUTNÁ (203 Czech Republic, guarantor, belonging to the institution), David POTĚŠIL (203 Czech Republic, belonging to the institution), Lenka TESAŘOVÁ (203 Czech Republic, belonging to the institution), Michaela POTĚŠILOVÁ (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, belonging to the institution) and Jiří MAYER (203 Czech Republic, belonging to the institution)
Edition
54th ASH Annual Meeting and Exposition, 2012
Other information
Language
English
Type of outcome
Konferenční abstrakt
Field of Study
30200 3.2 Clinical medicine
Country of publisher
United States of America
Confidentiality degree
není předmětem státního či obchodního tajemství
Impact factor
Impact factor: 9.060
RIV identification code
RIV/00216224:14330/12:00057983
Organization unit
Faculty of Informatics
ISSN
UT WoS
000314049600371
Keywords (in Czech)
chronická myeloidní leukemie; imatinib; dasatinib
Keywords in English
Chronic Myeloid Leukemia; Imatinib; Dasatinib
Tags
Změněno: 2/1/2013 11:48, Mgr. Pavel Šimara, Ph.D.
Abstract
V originále
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.
Links
| GBP302/12/G157, research and development project |
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| MSM0021622430, plan (intention) |
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