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, Michaela POTĚŠILOVÁ, Zbyněk ZDRÁHAL and Jiří MAYER. Apoptosis in Chronic Myeloid Leukemia Cells Transiently Treated with Imatinib or Dasatinib Is Caused by Residual BCR-ABL Kinase Inhibition. Online. In 54th ASH Annual Meeting and Exposition. 2012. ISSN 1528-0020. [citováno 2024-04-24]

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

• Original language: English
• Type of outcome: Conference abstract
• Field of Study: 30200 3.2 Clinical medicine
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: ASH Abstracts, Blood, November 16, 2012, Volume 120, Issue 21
• Impact factor: Impact factor: 9.060
• RIV identification code: RIV/00216224:14330/12:00057983
• Organization unit: Faculty of Informatics
• ISSN: 1528-0020
• UT WoS: 000314049600371
• Keywords (in Czech): chronická myeloidní leukemie; imatinib; dasatinib
• Keywords in English: Chronic Myeloid Leukemia; Imatinib; Dasatinib
• Tags: cbia-web

Abstract

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: Name: Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii

Investor: Czech Science Foundation

• MSM0021622430, plan (intention): Name: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Investor: Ministry of Education, Youth and Sports of the CR, Functional and molecular characteristics of cancer and normal stem cells - identification of targets for novel therapeutics and therapeutic strategies