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Abnormalities of GATA-1 in megakaryocytes from patients with idiopathic myelofibrosis.

Authors: Vannucchi, AM  Pancrazzi, A  Guglielmelli, P  Di Lollo, S  Bogani, C  Baroni, G  Bianchi, L  Migliaccio, AR  Bosi, A  Paoletti, F 
Citation: Vannucchi AM, etal., Am J Pathol. 2005 Sep;167(3):849-58.
Pubmed: (View Article at PubMed) PMID:16127162
DOI: Full-text: DOI:10.1016/S0002-9440(10)62056-1

The abnormal megakaryocytopoiesis associated with idiopathic myelofibrosis (IM) plays a role in its pathogenesis. Because mice with defective expression of transcription factor GATA-1 (GATA-1(low) mutants) eventually develop myelofibrosis, we investigated the occurrence of GATA-1 abnormalities in IM patients. CD 34(+) cells were purified from 12 IM patients and 8 controls; erythroblasts and megakaryocytes were then obtained from unilineage cultures of CD 34(+) cells. Purified CD 61(+), GPA(+), and CD 34(+) cells from IM patients contained levels of GATA-1, GATA-2, and FOG-1 mRNA, as well as of GATA-2 protein, that were similar to controls. In contrast, CD 61(+) cells from IM patients contained significantly reduced GATA-1 protein. Furthermore, 45% of megakaryocytes in biopsies from IM patients did not stain with anti-GATA-1 antibody, as compared to controls (2%), essential thrombocythemia (4%), or polycythemia vera (11%) patients. Abnormalities in immunoreactivity for FOG-1 were not found, and no mutations in GATA-1 coding sequences were found. The presence of GATA-1(neg) megakaryocytes in bone marrow biopsies was independent of the Val 617 Phe JAK 2 mutation, making it unlikely that a downstream functional relationship exists. We conclude that megakaryocytes from IM patients have reduced GATA-1 content, possibly contributing to disease pathogenesis as in the GATA-1(low) mice and also representing a novel IM-associated marker.


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CRRD Object Information
CRRD ID: 10450748
Created: 2016-01-20
Species: All species
Last Modified: 2016-01-20
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.