Apoptosis in chronic myeloid leukemia cells transiently treated
with imatinib or dasatinib is caused by residual BCR-ABL kinase
inhibition.

J 2013

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; Stanislav STEJSKAL; Irena KRONTORÁD KOUTNÁ; David POTĚŠIL; Lenka TESAŘOVÁ; Michaela POTĚŠILOVÁ; Zbyněk ZDRÁHAL a Jiří MAYER

Vydání

American Journal of Hematology, NJ 07030-577 United States, John Wiley & Sons, 2013, 0361-8609

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

PubMed

Impakt faktor

Impact factor: 3.477

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14330/13:00066079

Organizační jednotka

Fakulta informatiky

DOI

https://doi.org/10.1002/ajh.23419

UT WoS

000318043500423

Klíčová slova anglicky

Chronic Myeloid Leukemia; Imatinib; Dasatinib

Štítky

cbia-web, podil

Změněno: 29. 3. 2019 14:00, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Transient, potent BCR-ABL inhibition with tyrosine kinase inhibitors (TKIs) was recently demonstrated to be sufficient to commit chronic myeloid leukemia (CML) cells to apoptosis irreversibly. This mechanism explains the clinical efficacy of once-daily dasatinib treatment, despite the rapid clearance of the drug from the plasma. However, our in vitro data suggest that apoptosis induction after transient TKI treatment, observed in the BCR-ABL-positive cell lines K562, KYO-1, and LAMA-84 and progenitor cells from chronic phase CML patients, is instead caused by a residual kinase inhibition that persists in the cells as a consequence of intracellular drug retention. High intracellular concentrations of imatinib and dasatinib residues were measured in transiently treated cells. Furthermore, the apoptosis induced by residual imatinib or dasatinib from transient treatment could be rescued by washing out the intracellularly retained drugs. The residual kinase inhibition was also undetectable by the phospho-CRKL assay. These findings confirm that continuous target inhibition is required for the optimal efficacy of kinase inhibitors.

Návaznosti

CZ.1.05/1.1.00/02.0068, interní kód MU

Název: CEITEC - středoevropský technologický institut (Akronym: CEITEC)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC - středoevropský technologický institut, 1.1 Evropská centra excelence

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

Přiložené soubory

ZVV_2013_28_1094552.pdf

Požádat o autorskou verzi souboru

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. American Journal of Hematology. NJ 07030-577 United States: John Wiley & Sons, 2013, roč. 88, č. 5, s. 385-393. ISSN 0361-8609. Dostupné z: https://doi.org/10.1002/ajh.23419.

@article{1094552,
   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},
   article_location = {NJ 07030-577 United States},
   article_number = {5},
   doi = {https://doi.org/10.1002/ajh.23419},
   keywords = {Chronic Myeloid Leukemia; Imatinib; Dasatinib},
   language = {eng},
   issn = {0361-8609},
   journal = {American Journal of Hematology},
   title = {Apoptosis in chronic myeloid leukemia cells transiently treated with imatinib or dasatinib is caused by residual BCR-ABL kinase inhibition.},
   url = {http://www.ncbi.nlm.nih.gov/pubmed/23420553},
   volume = {88},
   year = {2013}
}

TY  - JOUR
ID  - 1094552
AU  - Šimara, Pavel - Stejskal, Stanislav - Krontorád Koutná, Irena - Potěšil, David - Tesařová, Lenka - Potěšilová, Michaela - Zdráhal, Zbyněk - Mayer, Jiří
PY  - 2013
TI  - Apoptosis in chronic myeloid leukemia cells transiently treated with imatinib or dasatinib is caused by residual BCR-ABL kinase inhibition.
JF  - American Journal of Hematology
VL  - 88
IS  - 5
SP  - 385-393
EP  - 385-393
PB  - John Wiley & Sons
SN  - 03618609
KW  - Chronic Myeloid Leukemia
KW  - Imatinib
KW  - Dasatinib
UR  - http://www.ncbi.nlm.nih.gov/pubmed/23420553
L2  - http://www.ncbi.nlm.nih.gov/pubmed/23420553
N2  - Transient, potent BCR-ABL inhibition with tyrosine kinase inhibitors (TKIs) was recently demonstrated to be sufficient to commit chronic myeloid leukemia (CML) cells to apoptosis irreversibly. This mechanism explains the clinical efficacy of once-daily dasatinib treatment, despite the rapid clearance of the drug from the plasma. However, our in vitro data suggest that apoptosis induction after transient TKI treatment, observed in the BCR-ABL-positive cell lines K562, KYO-1, and LAMA-84 and progenitor cells from chronic phase CML patients, is instead caused by a residual kinase inhibition that persists in the cells as a consequence of intracellular drug retention. High intracellular concentrations of imatinib and dasatinib residues were measured in transiently treated cells. Furthermore, the apoptosis induced by residual imatinib or dasatinib from transient treatment could be rescued by washing out the intracellularly retained drugs. The residual kinase inhibition was also undetectable by the phospho-CRKL assay. These findings confirm that continuous target inhibition is required for the optimal efficacy of kinase inhibitors.
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. \textit{American Journal of Hematology}. NJ 07030-577 United States: John Wiley \&{} Sons, 2013, roč.~88, č.~5, s.~385-393. ISSN~0361-8609. Dostupné z: https://doi.org/10.1002/ajh.23419.

Přehled o publikaci