Plasma levels of angiogenic factors and circulating endothelial cells in essential thrombocythemia: correlation with cytoreductive therapy and JAK2-V617F mutational status.
Recent studies have shown that angiogenesis plays an important role in the biology of hematological malignancies including essential thrombocythemia (ET). Using cytofluorimetric analysis, the levels of angiogenic factors, as well as the number of circulating endothelial cells (CECs), were determined in 65 patients with ET, including 33 previously untreated and 32 receiving cytoreductive therapy. Correlations between markers of angiogenesis and JAK2-V617F mutational status were also assessed. We found significantly higher levels of vascular endothelial growth factor (VEGF) and markedly decreased levels of placental growth factor in untreated patients with ET with respect to control subjects. VEGF levels were significantly increased in patients with white blood count >8.7 (x 10(9)/L) vs. <8.7 (x 10(9)/L). Furthermore, the levels of VEGF in patients on hydroxyurea (HU) therapy were markedly lower than in untreated patients. It was also demonstrated that the number of all CEC subpopulations (resting, activated, apoptotic, and circulating precursor endothelial cells) was increased in patients with ET in relation to controls, regardless of the JAK2-V617F status, and was not affected by cytoreductive treatment. In conclusion, our study highlights the possible role of angiogenesis in the pathophysiology of ET. It provides evidence that the number of CECs is elevated independently of JAK2-V617F status and is not down-regulated by HU or anagrelide therapy. Our data suggest that VEGF levels are particularly elevated in patients with high leukocytosis. Further investigation should be undertaken to determine the possible role of antiangiogenic therapy in ET.
Treliński
Jacek
J
Department of Hematology, Medical University of Łódź, Copernicus Memorial Hospital, Łódź, Poland. jtrel2001@yahoo.com
Wierzbowska
Agnieszka
A
Krawczyńska
Anna
A
Sakowicz
Agata
A
Pietrucha
Tadeusz
T
Smolewski
Piotr
P
Robak
Tadeusz
T
Chojnowski
Krzysztof
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042501:Angiogenic Proteins / Q000097:blood*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D000072483:Placenta Growth Factor; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011257:Pregnancy Proteins / Q000097:blood; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D042501:Angiogenic Proteins; D000970:Antineoplastic Agents; C000608036:PGF protein, human; D011257:Pregnancy Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D006918:Hydroxyurea