GATA-1 and erythropoietin receptor genes are highly expressed in erythroleukemia

We examined expression of the erythroid-associated genes GATA-1 and erythropoietin receptor (EPOR) in primary leukemia using the reverse transcriptase-polymerase chain reaction (RT-PCR). GATA-1 and EPOR mRNAs were detectable in all casts of erythroleukemia (French-American-British classification: M6) or early erythroblastic leukemia. In all other leukemia casts, including M2 through M5, stem cell leukemia, and adult T-cell leukemia, these gene transcripts were undetectable. GATA-2 was detectable in all the cases of primary leukemias examined in this study, except one case of M5. In one case, the phenotype switched from myeloid (M2) to erythroid (M6) and then back to myeloid. Northern blotting and RT-PCR revealed that GATA-1 and EPOR mRNAs were significantly upregulated at the M6 stage compared with the M2 stage. GATA-1 may be involved in the expression of an erythroid phenotype in acute leukemia. We generated HL-60 transfectants exogenously expressing GATA-1. The majority of HL-60 cells expressing GATA-1 lacked azurophilic granules, and electron microscopic analysis revealed that myeloperoxidase activity was negative. Platelet peroxidase activity, which was detectable in both megakaryoblasts and erythroid progenitors, was positive. However, EPOR and glycophorin A mRNAs were undetectable by RT-PCR. These findings suggest that besides GATA-1, a third factor may be required for the expression of mature erythroid phenotypes. In addition, our results indicate that GATA-1 is involved in inactivation of myeloperoxidase and activation of the platelet peroxidase.