BACKGROUND: The BCR-ABL negative myeloproliferative neoplasms, polycythaemia vera, essential thrombocythaemia (ET) and myelofibrosis (MF) are characterised by mutations in JAK2, CALR or MPL. However, a yet unknown factor drives the precise disease phenotype. The haematopoietic transcription factor GATA-1 and its downstream targets NFE2 and FLI1 are responsible for determining erythroid and megakaryocyte lineages during haematopoietic stem cell differentiation. Previous studies have demonstrated low level of GATA-1 expression in megakaryocytes from patients with myelofibrosis.
OBJECTIVES AND METHODS: The expression of GATA-1, NFE2, and FLI1, was studied for changes in the peripheral blood (PB) of ET patients. Peripheral blood samples were obtained from 36 ET patients, 14 patients with MF and 7 healthy control donors. Total RNA from peripheral blood mononuclear cells (PBMCs) was extracted, and quantitative PCR was used to determine relative changes in gene expression. Protein levels of GATA-1 were also determined in bone marrow sections from ET and MF patients.
RESULTS: GATA-1 mRNA was upregulated in ET patients, regardless of treatment regimen or mutational status. The expression of FLI1 was significantly downregulated, whereas the expression of NFE2 was unaffected by changes in GATA-1 levels. Megakaryocytes from ET patients displayed increased protein levels of GATA-1 compared to MF patients.
CONCLUSIONS: Our results confirmed, in PB, our previous data demonstrating elevated levels of GATA-1 in total bone marrow of ET patients. GATA-1 levels are independent from cytoreductive therapies and may have utility as a diagnostic marker in ET and in its differential diagnosis from MF. This article is protected by copyright. All rights reserved.