Spontaneous δ- to β-globin switching in K562 human leukemia cells

Previous analysis of the hemoglobin phenotype of the K562 human erythroleukemia cell line showed regulated expression of the ε-, ζ-, γ-, α-, and δ-globin genes. Expression of the β-globin genes has not been previously detected in this cell line. In this report, we describe the isolation of a variant of the K562 cell line that actively expresses β-globin messenger RNA (mRNA) and polypeptide and shows greatly reduced expression of the δ-globin genes. This phenotype developed spontaneously in culture while two other K562 isolates grown under the same culture conditions have not undergone the same δ- to β-globin switch. Analysis of this unique K562 variant shows that a construct containing a β-globin promoter is quite active upon transient transfection into these cells. This finding suggests that the activation of the endogenous β-globin genes results from changes in the trans-acting environment of these cells. The regulation of the β-globin genes in this variant is characterized by a paradoxical decrease in the level of β-globin mRNA after exposure to hemin. Other globin genes of this variant are appropriately regulated and show increased expression after hemin induction. Further study of this variant may shed light on mechanisms of gene regulation that are involved in hemoglobin switching.