ORIGINAL ARTICLES  TRENDS IN MOLECULAR DIAGNOSIS AND THERAPY OF β-THALASSEMIA AND SICKLE CELL ANEMIA 

Minerva Biotecnologica 2003 June;15(2):123-8

Copyright © 2003 EDIZIONI MINERVA MEDICA

language: English

The human erythroleukemia K562 cell culture system for identification of inducers of fetal hemoglobin

Gambari R. ^{1, 2}

¹ Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy; ² Laboratory for the Development of Pharmacological and Pharmacogenomic Therapy of Thalassemia, Biotechnology Center, University of Ferrara, Ferrara, Italy

The ­human leu­kem­ic K562 ­cell ­line has ­been pro­posed as a use­ful in ­vitro mod­el to ­study the molec­u­lar mech­a­nism(s) reg­u­lat­ing the expres­sion of the ­human embryon­ic and ­fetal glo­bin ­genes, as ­well as to deter­mine the ther­a­peu­tic poten­tial of new dif­fe­ren­ti­a­tion-induc­ing com­pounds. This ­cell ­line exhib­its a low pro­por­tion of hemo­glo­bin (Hb) syn­the­siz­ing ­cells ­under stan­dard ­cell ­growth con­di­tions, but it is ­capable of under­go­ing eryth­roid dif­fe­ren­ti­a­tion ­when treat­ed ­with a varie­ty of com­pounds, ­such as hem­in, cyto­sine ara­bin­o­side (ara-C), butyr­ic ­acid, 5-aza­cy­ti­dine, chro­mo­my­cin and mith­ram­y­cin, tal­li­mus­tine, cis­pla­tin and cis­pla­tin ana­logs. Following eryth­roid induc­tion of K562 ­cells, Hb Portland (ζ2γ2) and Hb Gower 1 (ζ2ε2) accu­mu­late, due to ­increase in the expres­sion of ­human ζ-, ε- and γ-glo­bin ­genes. K562 ­cells are suit­able for iden­ti­fy­ing induc­ers of ­fetal hemo­glo­bin (HbF). However, ­after a pre­lim­i­nary screen­ing, the mole­cules ­able to ­induce eryth­roid dif­fer­en­tia­tion of K562 ­cells ­should be test­ed in the 2-phas­es cul­ture ­systems of ­human eryth­roid pre­cur­sors ­from periph­er­al ­blood, to ­obtain ­more infor­ma­tive ­results on the ­effects of induc­ers on HbF pro­duc­tion.