GATA-1 AND ERYTHROPOIETIN RECEPTOR GENES ARE HIGHLY EXPRESSED IN ERYTHROLEUKEMIA

We examined expression of the erythroid-associated genes GATA-1 and er ythropoietin receptor (EPOR) in primary leukemia using the reverse tra nscriptase-polymerase chain reaction (RT-PCR). GATA-1 and EPOR mRNAs w ere detectable in all casts of erythroleukemia (French-American-Britis h classification: M6) or early erythroblastic leukemia. In all other l eukemia 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 stud y, except one case of M5. In one case, the phenotype switched from mye loid (M2) to erythroid (M6) and then back to myeloid. Northern blottin g and RT-PCR revealed that GATA-1 and EPOR mRNAs were significantly up regulated at the M6 stage compared with the M2 stage. GATA-1 may be in volved in the expression of an erythroid phenotype in acute leukemia. We generated HL-60 transfectants exogenously expressing GATA-1. The ma jority of HL-60 cells expressing GATA-1 lacked azurophilic granules, a nd electron microscopic analysis revealed that myeloperoxidase activit y 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 findi ngs suggest that besides GATA-1, a third factor may be required for th e expression of mature erythroid phenotypes. In addition, our results indicate that GATA-1 is involved in inactivation of myeloperoxidase an d activation of the platelet peroxidase.