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Title of Journal: Int J Hematol

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Abbravation: International Journal of Hematology

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Springer Japan

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DOI

10.1002/jsfa.2740130102

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1865-3774

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Increase in γglobin mRNA content in human erythro

Authors: Ilaria Lampronti Nicoletta Bianchi Cristina Zuccato Francesco Dall’Acqua Daniela Vedaldi Giampietro Viola Rocco Potenza Francesco Chiavilli Giulia Breveglieri Monica Borgatti Alessia Finotti Giordana Feriotto Francesca Salvatori Roberto Gambari
Publish Date: 2009/09/25
Volume: 90, Issue: 3, Pages: 318-327
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Abstract

The aim of the present study was to identify molecular analogs of angelicin ANG able to increase erythroid differentiation of K562 cells and expression of γglobin genes in human erythroid precursor cells with low effects on apoptosis ANGlike molecules are wellknown photosensitizers largely used for their antiproliferative activity in the treatment of different skin diseases ie psoriasis vitiligo eczema and mycosis fungoides To verify the activity of these derivatives we employed three experimental cell systems 1 the human leukemic K562 cell line 2 K562 cell clones stably transfected with a pCCL construct carrying greenEGFP under the γglobin gene promoter and 3 the twophase liquid culture of human erythroid progenitors isolated from normal donors and βthalassemia patients The results of our study suggest that trimethyl ANG is a powerful inducer of erythroid differentiation compared with known inducers such as ANG cytosine arabinoside mithramycin and cisplatin These data could have practical relevance because pharmacologically mediated regulation of human γglobin gene expression with the consequent induction of fetal hemoglobin is considered a potential therapeutic approach in hematological disorders including βthalassemia and sickle cell anemiaRG is granted by AIRC Fondazione Cariparo Cassa di Risparmio di Padova e Rovigo Cofin2005 by STAMINA Project University of Ferrara by UE ITHANET Project and by Telethon Project GGP07257 This research was also supported by Regione Emilia–Romagna Spinner Project and by Associazione Veneta per la Lotta alla Talassemia Rovigo

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