Involvement of transforming growth factor-beta and thrombopoietin in the pathogenesis of myelodysplastic syndrome with myelofibrosis.
We investigated the cause of myelofibrosis and proliferation of megakaryocytes in myelodysplastic syndrome with myelofibrosis (MDS-MF (+)). Plasma-transforming growth factor-beta1 (PTGF-beta1) 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-beta1 mRNA than those from IMF, MDS-MF (-) or HV. When we immunostained bone marrow specimens of MDS-MF (+) for TGF-beta, 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-beta1 levels, respectively, in each disease. Thus, in MDS-MF (+), both myelofibrosis and the increased megakaryocytes were ascribed to overproduction of TGF-beta1 from blasts.
Akiyama
T
T
Fourth Department of Internal Medicine, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido, Japan.
Matsunaga
T
T
Terui
T
T
Miyanishi
K
K
Tanaka
I
I
Sato
T
T
Kuroda
H
H
Takimoto
R
R
Takayama
T
T
Kato
J
J
Yamauchi
N
N
Kogawa
K
K
Sakamaki
S
S
Hirayama
Y
Y
Kohda
K
K
Niitsu
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000096:biosynthesis / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000473:pathology; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D055728:Primary Myelofibrosis / Q000150:complications / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D013926:Thrombopoietin / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*
D018952:Antigens, CD34; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013926:Thrombopoietin