No abstract

The aim of this study was to perform an immunohistochemical analysis from 100 megakaryocytes per sample, analyzing positivity and intensity levels of anti-LAP human TGF-β1 (or Latent TGF-β1) and anti-TGF-β1 (or Active TGF-β1) antibodies from 18 essential thrombocythemia (ET) and 38 primary myelofibrosis (PMF) patients (being 19 pre-fibrotic and 19 fibrotic). Six bone marrow donor biopsies were used as controls. Fibrosis in bone marrow biopsies (BMB) was evaluated according to the European Consensus. The average fibrosis grade differed between each group (P=0.001 or P=0.003). Latent TGF-β1 values differed significantly between pre-fibrotic (P=0.018) and fibrotic (P=0.031) groups when compared with the control group. The high immunoexpression level of Latent TGF-β1 in the megakaryocytes from patients with myelofibrosis, which was not observed in patients with essential thrombocythemia, may be associated with the development of bone marrow fibrosis.

No abstract

Experiments were undertaken to assess the role of amifostine in the activation of latent TGF␤1 and in the smad proteins cascade (smad 2/3, smad4, smad7), focusing on megakaryocytes, in the bone marrow irradiated in vivo. Non-irradiated megakaryocytes were negative for active TGF␤1. Immunopositivity to active TGF␤1 was detected in megakaryocytes 10 days after irradiation in amifostine-treated and untreated marrows. Smad 2/3 and smad 4 were strongly positive in the nucleus of megakaryocytes 10 days after irradiation. At the same time, a predominant hypocellular bone marrow with foci of hematopoiesis was observed with few megakaryocytes. An increase in the number of reticulin fibers was also seen. In amifostine-treated marrows, smad 2/3 and smad4 were not detected in the nucleus but were positive in the cytoplasm of megakaryocytes 10 days after irradiation. Coincidentally, bone marrows were cellular with megakaryocytes. Smad7 immunoexpression was detected in the cytoplasm of megakaryocytes in the non-irradiated, amifostine-treated and in the irradiated, amifostine-treated marrows. Data indicate that amifostine does not prevent latent TGF␤1 activation in irradiated megakaryocytes. While TGF␤1 signal transduction occurs in megakaryocytes in untreated bone marrows, it is inhibited in megakaryocytes in amifostine-treated marrows due to the induction of smad 7 activation. This is the first report showing smad 7 activation by amifostine. Our results also suggest a role for TGF␤1 as an inhibitor of megakaryocytes in vivo. Am. J. Hematol. 71:143-151, 2002.

No abstract