Differential levels of soluble endoglin (CD105) in myeloid malignancies.
Angiogenesis contributes to disease progression in solid and hematopoietic malignancies, and endoglin (CD105), a component of the transforming growth factor (TGF)-beta receptor complex, is a powerful marker of neovascularization. Elevated amounts of soluble CD105 (sCD105) have been recently identified in selected solid tumors but no data are available on sCD105 in hematopoietic malignancies. Therefore, levels of sCD105 were investigated in sera of patients with acute myeloid leukemia (AML) (n = 10) or chronic myeloproliferative disorders (CMD) (n = 28), and correlated with those of soluble TGF-beta(1) (sTGF-beta(1)). Dot blot assay detected higher amounts of sCD105 (P < 0.05) both in AML (4.34 +/- 2.62 OD/mm(2)) and in CMD (3.71 +/- 2.09 OD/mm(2)) patients than in healthy subjects (n = 14, 2.38 +/- 1.18 OD/mm(2)). Instead, enzyme-linked immunosorbent assay (ELISA) identified (P < 0.05) lower and higher levels of sTGF-beta(1) in AML (32,017 +/- 1,900 pg/ml) and CMD (60,700 +/- 19,200 pg/ml) patients, respectively, compared to healthy individuals (n = 11, 47,173 +/- 5,443 pg/ml). In essential thrombocythemia (ET) patients with thrombotic episodes, levels of sCD105 were lower (P < 0.05) compared to patients without thrombotic complications, and inversely correlated with those of sTGF-beta(1) (r = 0.94). Conversely, amounts of sCD105 directly correlated with levels of sTGF-beta(1) (r = 0.74) in ET patients without thrombotic events. Our results show that high levels of sCD105 are present in myeloid malignancies that are characterized by a high cellular proliferation rate, and suggest that an altered balance between sCD105 and sTGF-beta(1) might favor disease progression and clinical complications.
Calabrò
Luana
L
Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy.
Fonsatti
Ester
E
Bellomo
Giacomo
G
Alonci
Andrea
A
Colizzi
Francesca
F
Sigalotti
Luca
L
Altomonte
Maresa
M
Musolino
Caterina
C
Maio
Michele
M
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D002908:Chronic Disease; D000071063:Endoglin; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000378:metabolism*; D011956:Receptors, Cell Surface; D012995:Solubility; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1