Premium
Decrease of Smad4 gene expression in patients with essential thrombocythaemia may cause an escape from suppression of megakaryopoiesis by transforming growth factor‐ β 1
Author(s) -
Kuroda Hiroyuki,
Matsunaga Takuya,
Terui Takeshi,
Tanaka Ikuta,
Takimoto Rishu,
Fujikawa Koshi,
Takayama Tetsuji,
Kato Junji,
Hirayama Yasuo,
Sakamaki Sumio,
Kohda Kyuhei,
Niitsu Yoshiro
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04755.x
Subject(s) - transforming growth factor , megakaryocyte , thrombopoietin , growth factor , transfection , biology , medicine , cancer research , endocrinology , immunology , gene , microbiology and biotechnology , receptor , genetics , haematopoiesis , stem cell
Summary Essential thrombocythaemia (ET) is characterized by the abnormal and sustained proliferation of megakaryocytes. The mechanism for this lineage‐specific expansion in ET, remains unclear. We have previously reported that transforming growth factor‐ β 1 (TGF‐ β 1) is involved in negative feedback regulation of megakaryopoiesis in both healthy volunteers (HV) and patients with idiopathic thrombocytopenic purpura (ITP). The present study found that megakaryocyte colony‐forming units (CFU‐MK) of ET patients were less sensitive to TGF‐ β 1 than those of HV. The expression of Smad4 (Sma‐ and Mad‐related protein‐4) in CFU‐MK of ET patients was reduced in comparison with that of HV. Finally, to confirm that the impaired TGF‐ β 1 sensitivity was caused by reduced expression of Smad4, we examined Smad4‐transfected CFU‐MK from ET patients in the presence of TGF‐ β 1, and verified that the transfectants were indeed as susceptible as CFU‐MK from HV to TGF‐ β 1. Thus it was surmised that one of the mechanisms for impaired sensitivity of CFU‐MK to TGF‐ β 1 is the reduced expression of Smad4.