Expression of human alpha-globin genes in hybrid mouse erythroleukaemia cells depends on differentiated state of human donor cell.

We have developed a system which can be used to study the mechanisms that may govern the expression of human alpha-globin genes in human erythroid and non-erythroid haematopoietic cells. Human chromosome 16, which has been shown to bear the human alpha-globin genes, is introduced by cell fusion into mouse erythroleukemia (MEL) cells to generate continuously proliferating cell lines that retain permanently the human alpha-globin genes. We have shown that hybrid diploid MEL cells with human alpha-globin genes from erythroid donor cells express these genes fully through globin chain synthesis, while hybrid diploid MEL cells containing human alpha-globin genes from non-erythroid human haematopoietic donor cells contain very low levels of human alpha-globin mRNA and no detectable human alpha-globin chains. The levels of human alpha-globin mRNA in these hybrid cells were found to depend on factors present in the MEL recipient cell as well as on the differentiated state of the human donor cell, suggesting that this system may be suitable for characterisation of mechanisms governing haematopoietic differentiation in man.