HUMAN LEUKEMIA K562 CELLS - INDUCTION TO ERYTHROID-DIFFERENTIATION BYGUANINE, GUANOSINE AND GUANINE-NUCLEOTIDES

Background and Objective. Human leukemic K562 cells are able to underg o erythroid differentiation in vitro when cultured with a variety of i nducers, leading to increased expression of embryo-fetal globin genes such as the zeta, epsilon and gamma-globin genes. Therefore the K562 c ell line has been proposed as a very useful in vitro model system for determining the therapeutical potential of new differentiating compoun ds as well as for studying the molecular mechanism(s) that regulate ch anges in the expression of embryonic and fetal human globin genes. In this study we explored whether nucleoside triphosphates and related co mpounds are able to induce differentiation of K562 cells. Methods. K56 2 cell differentiation was studied using the benzidine test; hemoglobi ns were characterized by cellulose acetate gel electrophoresis and mRN A accumulation was investigated by Northern blot analysis. Results. Th e main conclusion of this paper is that guanine, guanosine and guanine ribonucleotides are effective inducers of K562 cell differentiation. Expression of both Hb Portland and Hb Cower 1 is increased in CTP-indu ced K562 cells. This increase is associated with greater gamma-globin mRNA accumulation. By contrast, ATP, CTP and UTP are not able to induc e erythroid differentiation. Interpretaton and Conclusions. These find ings suggest that guanine, guanosine and guanine ribonucleotides are i nducers of erythroid differentiation of K562 cells. This is of some re levance since differentiating compounds have been proposed as antitumo r agents. In addition, inducers of erythroid differentiation that stim ulate gamma-globin synthesis might be considered in the experimental t herapy of hematological diseases associated with a failure in the expr ession of adult beta-globin genes. (C) 1997, Ferrata Stouti Foundation .