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

Am J Pathol. 2005 Sep;167(3):849-58. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / metabolism
  • Case-Control Studies
  • Cells, Cultured
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Erythroid-Specific DNA-Binding Factors
  • Female
  • GATA1 Transcription Factor
  • Humans
  • Immunohistochemistry / methods
  • Integrin beta3 / metabolism
  • Male
  • Megakaryocytes / metabolism*
  • Megakaryocytes / pathology
  • Polycythemia Vera / metabolism
  • Polycythemia Vera / pathology
  • Primary Myelofibrosis / metabolism*
  • Primary Myelofibrosis / pathology
  • Staining and Labeling
  • Thrombocytosis / metabolism
  • Thrombocytosis / pathology
  • Transcription Factors / deficiency*
  • Transcription Factors / immunology
  • Transcription Factors / metabolism


  • Antibodies
  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • Integrin beta3
  • Transcription Factors