Use this url to cite publication: https://hdl.handle.net/20.500.12512/113447
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The Exploration of PI3K/Akt/mTOR, JAK/STAT, and Hedgehog pathways inhibitor effect on CALR Del52 cells proliferation / Roberta Vadeikienė, Baltramiejus Jakštys, Rasa Ugenskienė, Saulius Šatkauskas, Elona Juozaitytė
Type of publication
Tezės kitame recenzuojamame leidinyje / Theses in other peer-reviewed publication (T1e)
Author(s)
Lietuvos sveikatos mokslų universitetas | ||
Jakštys, Baltramiejus | Vytauto Didžiojo universitetas | |
Šatkauskas, Saulius | Vytauto Didžiojo universitetas | |
Title
The Exploration of PI3K/Akt/mTOR, JAK/STAT, and Hedgehog pathways inhibitor effect on CALR Del52 cells proliferation / Roberta Vadeikienė, Baltramiejus Jakštys, Rasa Ugenskienė, Saulius Šatkauskas, Elona Juozaitytė
Publisher (trusted)
Lithuanian University of Health Sciences |
Date Issued
Date Issued |
---|
2022-04-06 |
Extent
p. 24-25.
Is part of
Health for All: 2022 - International Conference Health for All “Our planet, our health” : abstract book : Kaunas, Lithuania, 6-7 April, 2022 / [organised: Doctoral Student’s committee of Lithuanian University of Health Sciences]. Kaunas : Lithuanian University of Health Sciences, 2022.
Version
Originalus / Original
Description
Experimental medicine
Bibliogr.: p. 25
Field of Science
Abstract
Introduction BCR-ABL1-negative classic myeloproliferative neoplasms (MPN) include primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Calreticulin (CALR) 52 bp deletion and 5 bp insertion were discovered to be involved in MPN pathogenesis. Calreticulin, a Ca2+-binding chaperone, is implicated in the regulation of Ca2+, protein folding, and avariety of signaling pathways. It was reported that mutant CALR results increased JAK/STAT and other signaling pathways activation. However, these data contrast with another study‘s observation that CALR mutant cells are not dependent on JAK/STAT signaling. Therefore, there is still a need to explore molecular mechanisms activated in CALR mutant cells. Aim The aim of our study was to characterize the effects of specific JAK/STAT, PI3K/Akt/mTOR, and Hedgehog signaling inhibitors in CALR Del52 mutated cells. Methods The UT-7 cell line was employed in our study. CRISPR/Cas9 system was chosen for CALR 52 bp deletion initiation in cells. After selection of potential DNA targets in gDNA, corresponding tabs were cloned into a vector (pSpCas9(BB)-2A-Puro (PX459) V2.0) that is optimized for Cas9and RNA-guided expression in eukaryotic cells. For plasmid and HDR template electrotransfer into UT-7 cells, the following parameters were applied: 1 HV pulse of 1600 V/cm with 500 µspulse duration (the electroporation system BTX T820 was used). The transfected cells weres elected in puromycin (1 μg/ml). Further, we explored the potent effect of targeting JAK/STAT, PI3K/Akt/mTOR, and Hedgehog pathways with specific agents in CALR Del52mutant and CALR WT cells. We evaluated the effect of CYT387 (JAK1/2 inhibitor), RAD001(mTOR inhibitor), and HPI-1 (Gli1/2 inhibitor) agents. The effect of signaling pathways [...].
Type of document
type::text::conference output::conference proceedings::conference paper
ISSN (of the container)
2669-1507
Other Identifier(s)
(LSMU ALMA)991575220707106
Coverage Spatial
Lietuva / Lithuania (LT)
Language
Anglų / English (en)
Bibliographic Details
5