Premium
GATA ‐1: A potential novel biomarker for the differentiation of essential thrombocythemia and myelofibrosis
Author(s) -
Lally James,
Boasman Kristian,
Brown Lilia,
Martinelli Vincenzo,
Cappuccio Ilaria,
Sovani Vishaka,
Marinaccio Christian,
Crispino John D.,
Graham Ciaren,
Rinaldi Ciro
Publication year - 2019
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14433
Subject(s) - essential thrombocythemia , polycythemia vera , myelofibrosis , haematopoiesis , megakaryocyte , megakaryocytopoiesis , gata1 , cancer research , bone marrow , biology , medicine , immunology , stem cell , genetics
Essentials The BCR‐ABL negative myeloproliferative neoplasms are subjected to unknown phenotypic modifiers. GATA‐1 is upregulated in ET patients, regardless of treatment regimen or mutational status. Myelofibrosis (MF) megakaryocytes displayed decreased GATA‐1 staining. GATA‐1 may have utility as a diagnostic marker in ET and in its differential diagnosis from MF.Abstract Background The BCR ‐ ABL ‐negative myeloproliferative neoplasms, i.e., polycythemia vera, essential thrombocythemia ( ET ), and myelofibrosis ( MF ), are characterized by mutations in JAK 2 , CALR , or MPL . However, an as yet unknown factor drives the precise disease phenotype. The hematopoietic transcription factor GATA‐1 and its downstream targets NFE2 and FLI1 are responsible for determining erythroid and megakaryocyte lineages during hematopoietic stem cell differentiation. Previous studies have demonstrated a low level of GATA ‐1 expression in megakaryocytes from patients with MF . Objectives and methods The expression of GATA ‐1 , NFE 2 and FLI 1 was studied for changes in the peripheral blood ( PB ) of ET patients. Peripheral blood samples were obtained from 36 ET patients, 14 MF patients, and seven healthy control donors. Total RNA from PB mononuclear cells ( PBMC s) was extracted, and quantitative polymerase chain reaction 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 m RNA was upregulated in ET patients, regardless of treatment regimen or mutational status. FLI 1 expression was significantly downregulated, whereas NFE 2 expression was unaffected by changes in GATA ‐1 m RNA levels. Megakaryocytes from ET patients showed increased protein levels of GATA ‐1 as compared with those from MF patients. Conclusions Our results confirmed, in PB , our previous data demonstrating elevated levels of GATA ‐1 m RNA in total bone marrow of ET patients. GATA ‐1 m RNA levels are independent of cytoreductive therapies, and may have utility as a diagnostic marker in ET and in its differential diagnosis from MF .