Involvement of transforming growth factor-β and thrombopoietin in the pathogenesis of myelodysplastic syndrome with myelofibrosis.

Akiyama, T.; Matsunaga, T.; Terui, T.; Miyanishi, K.; Tanaka, I.; Sato, T.; Kuroda, H.; Takimoto, R.; Takayama, T.; Kato, J.; Yamauchi, N.; Kogawa, K.; Sakamaki, S.; Hirayama, Y.; Kohda, K.; Niitsu, Y.

We investigated the cause of myelofibrosis and proliferation of megakaryocytes in myelodysplastic syndrome with myelofibrosis (MDS-MF ( )). Plasma-transforming growth factor-β1 (PTGF-β1) concentrations closely correlated with myelofibrosis grade in MDS-MF ( ) and were higher than those in idiopathic myelofibrosis (IMF), essential thrombocythemia (ET), idiopathic thrombocytopenic purpura (ITP), MDS-without MF (MDS-MF (−)) or healthy volunteers (HV). Peripheral blood mononuclear cells from MDS-MF ( ) patients expressed more TGF-β1 mRNA than those from IMF, MDS-MF (−) or HV. When we immunostained bone marrow specimens of MDS-MF ( ) for TGF-β, the intensity of blasts was apparently higher than that of megakaryocytes, while in MDS-MF (−), megakaryocytes were immunostained with a similar intensity as that in MDS-MF ( ), but blasts were negative for staining. In IMF, megakaryocytes, monocytes and small mononuclear cells representing CD34 cells were all similarly stained with a much lower intensity than that of blasts in MDS-MF ( ). The number of bone marrow megakaryocytes were increased the most in MDS-MF ( ), followed by ET, ITP, MDS-MF (−) and NHL and correlated with plasma thrombopoietin (TPO) levels or with plasma TGF-β1 levels, respectively, in each disease. Thus, in MDS-MF ( ), both myelofibrosis and the increased megakaryocytes were ascribed to overproduction of TGF-β1 from blasts.Leukemia (2005) 19, 1558–1566. doi:10.1038/sj.leu.2403875; published online 21 July 2005

MYELOFIBROSIS; BONE marrow; THROMBOPOIETIN; DYSPLASIA; THROMBOCYTOSIS; MESSENGER RNA

Leukemia (08876924), 2005, Vol 19, Issue 9, p1558

0887-6924

Academic Journal

10.1038/sj.leu.2403875