EUROPEAN JOURNAL OF
PHARMACEUTICAL AND MEDICAL RESEARCH

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)

European Journal of Pharmaceutical and Medical Research (EJPMR) has indexed with various reputed international bodies like : 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 , 

 ISSN 2394-3211

Impact Factor: 6.222

 ICV - 79.57

Abstract

ECTOPIC PLACENTAL-LIKE ALKALINE PHOSPHATASE (PLAP) REPROGRAMMING BY VITAMIN E IN CML BLAST CRISIS LEUKEMIC K562 CELLS

L. P. Shvachko*

ABSTRACT

Bagraund: Placental-like alkaline phosphatase (PLAP)-1ike enzymes are expressed by many tumors and can be detected in sera of patients with various cancers. Their ectopic expression has been considered to be potentially useful as tumor marker. Indeed, elevated levels of PLAP were found in 43% of seminomas and in 75% of recurrent metastatic tumors. However, the biological background of the role of this aberrant alkaline phosphatase in cancer progression is still unclear. We have focused on the study of the biological role of PLAP in leukemogenesis on the model of chronic myeloid leukemia (CML) K562 cells. Objective: The aim of the study was to attempt to use vitamin E for LSC reprogramming by inducing CEBP alpha (CCAAT/enhancer-binding protein α) and G-CSFR (granulocyte colony stimulating factor receptor) analyzing aberrant PLAP as biomarker of LSC phenotype. Methods: RNA extracted from K562 cells cultured with vitamin E was converted to for quantitative SYBR Green qRT-PCR analysis using primers to tissue nonspecific alkaline phosphatase (TNAP) and C/EBP alpha and G-CSFR respectively. Samples were cycled using the standard SYBR Green protocol on Q5 Bio-Rad StepOne qPCR instrument and analyzed using the comparative cycle threshold (CT) method to obtain relative mRNA expression. Amplicon (410 bp) was eluted from agarose gel (2.5%) and DNA- sequenced. Results: The progression of CML to blast crisis is correlated with both down-modulation of TNAP and C/EBP alpha as master regulator of granulocytic differentiation in myelopoesis. We have observed the ectopic expression of mRNA PLAP gene in K562 cells by real-time RT-PCR. We founded by sequencing that PLAP gene corresponds to embryonic type of placental alkaline phosphatase (EPLAP) and have no gene homology with tissue placental alkaline phosphatase (PAP) that was absent in K562. Vitamin E decreases the mRNA PLAP expression level and increases the mRNA TNAP gene expression. Moreover, along with down-regulation of aberrant PLAP and up-regulation of TNAP, vitamin E in a dose of 100 µM increases mRNA expression of transcription factor C/EBP alpha and G-CSFR. It was reported that osteoblast-expressed TNAP is a biomarker of HSCs and directly associated with HSC hematopoiesis in bone marrow (BM). We have proposed that loss of TNAP in BM HSC niche may contribute into CML pathogenesis, suggesting the impairment of bone marrow mesenchymal stem cell (BM MSC) – derived osteoblast differentiation. The aberrant PLAP in K562 cells seems to differ from tissue TNAP and tissue placental alkaline phosphatase. Conclusion. EPLAP may be considered as a putative target in differentiation therapies in myeloid leukemias. Our findings suggest the potential role of vitamin E in adjuvant therapy of lelukemia as the inducer of differentiation potential of K562 leukemic cells through decreasing ectopic EPLAP along with induction of granulopoiesis factors CEBP alpha/G-CSFR. We have declared that embryonic PLAP is pluripotent LSC-associated biomarker in contrast of TNAP as multipotent HSC-associated biomarker. Vitamin E may be putative modulator of LSCs reprogramming in biotherapies of CML.

Keywords: EPLAP may be considered as a putative target in differentiation therapies in myeloid leukemias.


[Full Text Article]

INDEXING

NEWS & UPDATION

  • New Issue Published

    Its Our pleasure to inform you that, EJPMR 1 August 2020 Issue has been Published, Kindly check it on http://www.ejpmr.com/home/current_issues

  • EJPMR AUGUST ISSUE PUBLISHED

    AUGUST 2020 Issue has been successfully launched on 1 August 2020.

  • EJPMR New Impact Factor

    Its our Pleasure to Inform you that EJPMR Impact Factor has been increased from  5.804 to 6.222, due to high quality Publication at International Level

  • Index Copernicus Value

    EJPMR Received Index Copernicus Value 79.57, due to High Quality Publication in EJPMR at International Level

  • Journal web site support Internet Explorer, Google Chrome, Mozilla Firefox, Opera, Saffari for easy download of article without any trouble.

    .

  • Article Invited for Publication

    Article are invited for publication in EJPMR Coming Issue

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