EUROPEAN JOURNAL OF
PHARMACEUTICAL AND MEDICAL RESEARCH

( An ISO 9001:2015 Certified International Journal )

An International Peer Reviewed Journal for Pharmaceutical, Medical & Biological Sciences

An Official Publication of Society for Advance Healthcare Research (Reg. No. : 01/01/01/31674/16)

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 ISSN 2394-3211

Impact Factor: 6.222

 ICV - 79.57

Abstract

VITAMIN E VERSUS IMATINIB TARGETS SNAIL -EMT PHENOTYPE IN CML BLAST CRISIS LEUKEMIC K562 CELLS IN VITRO

L. P. Shvachko*

ABSTRACT

Background.The BCR-ABL- positive chronic myeloid leukemia (CML) is leukemic stem cells (LSCs) disease undergoing EMT stemness phenotype development. Therefore, CML progression results in EMT stemnes -LSCs-derived undifferentiated blast cells crisis (BC-CML). Imatinib targeting CML marker p210BCR-ABL oncogene tyrosinekinase and acting as an ATP-competitive inhibitor of the ABL1 kinase domain recently is successfull in TKI- therapies with a long enough CML remission. But imatinib as well as a TKIs still leads to EMT stemness- derived resistance. The Aim is search for alternative mechanism in overcoming EMT-stemnes LSCs phenotype in CML blast crisis progression by Vitamin E in versus imatinib. The Methods. The CMLblast crisis leukemic K562 cells exposed by vitamin E (100 μM) and Imatinib (Glivek) (2,5 mM) under 48 h were studied on the mRNA gene expression level of transcription factor SNAIL, as key stemnes EMT-inductor and C/EBPα transcription factor as pivotal master regulator of myelopoiesis by real-time qRT-PCR assay. The Conclusion. On the date obtained we have elucidated the principal different mechanisms of relative increasing of C/EBPα mRNA expression in CML blast crisis K562 cells exposured by vitamin E and Imatinib (Glivek). The mechanism of action of vitamin E is associated with the reprogramming of the EMT-SNAIL phenotype in CML blast cells to differentiation potential while the action of Imatinib focuses only on the inhibition of BCR-ABL -tyrosine kinase in CML blast cells that resulting to derepression of the main target CEBPα myeloid differentiation factor. The obtained results can significantly supplement the mechanism of acquisition of Imatinib resistance through activation of SNAIL-EMT- leukemic stem cell phenotype in CML progression.

Keywords: chronic myeloid leukemia, imatinib-resistance, Snail - EMT stemness, vitamin E, myeloid master regulator C/EBP ?.


[Full Text Article]

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Google Scholar Indian Science Publications InfoBase Index (In Process) SOCOLAR, China Research Bible, Fuchu, Tokyo. JAPAN International Society for Research activity (ISRA) Scientific Indexing Services (SIS) Polish Scholarly Bibliography Global Impact Factor (GIF) (Under Process) Universal Impact Factor International Scientific Indexing (ISI), UAE Index Copernicus CAS (A Division of American Chemical Society) USA (Under Process) Directory of Open Access Journal (DOAJ, Sweden, in process) UDLedge Science Citation Index CiteFactor Directory Of Research Journal Indexing (DRJI) Indian citation Index (ICI) Journal Index (JI, Under Process) Directory of abstract indexing for Journals (DAIJ) Open Access Journals (Under Process) Impact Factor Services For International Journals (IFSIJ) Cosmos Impact Factor Jour Informatics (Under Process) Eurasian Scientific Journal Index (ESJI) International Innovative Journal Impact Factor (IIJIF) Science Library Index, Dubai, United Arab Emirates Pubmed Database [NLM ID: 101669306] (Under Process) IP Indexing (IP Value 2.40) Web of Science Group (Under Process) Directory of Research Journals Indexing Scholar Article Journal Index (SAJI) International Scientific Indexing ( ISI ) Scope Database