Apoptosis in Chronic Myeloid Leukemia Cells Transiently Treated
with Imatinib or Dasatinib Is Caused by Residual BCR-ABL Kinase
Inhibition

a 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.

Základní údaje

Originální název

Apoptosis in Chronic Myeloid Leukemia Cells Transiently Treated with Imatinib or Dasatinib Is Caused by Residual BCR-ABL Kinase Inhibition

Autoři

ŠIMARA, Pavel (203 Česká republika, domácí), Stanislav STEJSKAL (203 Česká republika, domácí), Irena KRONTORÁD KOUTNÁ (203 Česká republika, garant, domácí), David POTĚŠIL (203 Česká republika, domácí), Lenka TESAŘOVÁ (203 Česká republika, domácí), Michaela POTĚŠILOVÁ (203 Česká republika, domácí), Zbyněk ZDRÁHAL (203 Česká republika, domácí) a Jiří MAYER (203 Česká republika, domácí)

Vydání

54th ASH Annual Meeting and Exposition, 2012

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

ASH Abstracts, Blood, November 16, 2012, Volume 120, Issue 21

Impakt faktor

Impact factor: 9.060

Kód RIV

RIV/00216224:14330/12:00057983

Organizační jednotka

Fakulta informatiky

ISSN

UT WoS

000314049600371

Klíčová slova česky

chronická myeloidní leukemie; imatinib; dasatinib

Klíčová slova anglicky

Chronic Myeloid Leukemia; Imatinib; Dasatinib

Štítky

cbia-web

Změněno: 2. 1. 2013 11:48, Mgr. Pavel Šimara, Ph.D.

Anotace

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.

Návaznosti

GBP302/12/G157, projekt VaV

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

Investor: Grantová agentura ČR, Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii

MSM0021622430, záměr

Název: Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Funkční a molekulární charakteristiky nádorových a normálních kmenových buněk - identifikace cílů pro nová terapeutika a terapeutické strategie

Citovat

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 54th ASH Annual Meeting and Exposition. 2012. ISSN 1528-0020.

@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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