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Title: Prevalence and significance of the c-KIT receptor expression and mutation in pediatric acute myeloid leukemia and the perspectives of c-KIT tyrosine kinase inhibitors application

Abstract:

The c-KIT receptor plays a crucial role in hematopoiesis. The c-KIT expression has been discovered on the healthy cells of the bone marrow and on the blastic cells in acute myeloid leukemia (AML). Activating mutations of the c-KIT gene could be responsible for triggering leukemogenesis.The aim of the doctoral dissertation was to investigate the prevalence and significance of the c-KIT expression and mutation in pediatric AML and to evaluate in vitro the influence of the selected tyrosine kinase inhibitors (i.e. imatinib, nilotinib, midostaurin,dasatinib and SEL24) on leukemic cells.The results of the conducted experiments revealed the expression of the c-KIT on all tested cell lines. In exon 17 point mutation was detected at codon N822 in the Kasumi-1 cell line. The experiments revealed that all investigated compounds inhibited the proliferation of AML cell lines in a dose- and time-dependent manner. Both differential staining and FACS analysis showed independently that all examined inhibitors induced apoptosis. Further, the results of the study showed a decreased level of phosphorylation of the c-KIT receptor and Akt and Erk1/2 kinases under the influence of the examined compounds.The results of the conducted study indicate that inhibitors of the receptor tyrosine kinases constitute an interesting and structurally diversified class of the potential anticancer compounds.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

hematologia ; pediatria

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Lekarski.

Promoter:

Walentyna Balwierz

Date issued:

2015

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:4089

Call number:

ZB-124224

ControlNumberVIRTUA:

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Language:

pol

Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

Object collections:

Last modified:

May 24, 2021

In our library since:

May 12, 2016

Number of object content hits:

13

Number of object content views in PDF format

12

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/4089

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ZB-124224 May 24, 2021
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