title: Circulating endothelial cells in essential thrombocythemia and polycythemia vera: correlation with JAK2-V617F mutational status, angiogenic factors and coagulation activation markers.
abstract: Angiogenesis plays an important role in the biology of hematological malignancies, including essential thrombocythemia (ET) and polycythemia vera (PV). Some data suggests that it has a role in the pathogenesis of thrombosis, the major clinical problem in ET and PV. The number of different subpopulations of circulating endothelial cells (CECs), plasma levels of vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor 1 and 2 (sVEGFR-1,2) and placenta growth factor (PlGF) were determined in 30 patients with ET and 16 patients with PV. Correlations between angiogenesis and JAK2-V617F mutational status, risk factors for thrombosis and coagulation activation markers were also assessed. The number of CEC subpopulations, were markedly higher in ET and PV patients, irrespective of JAK2-V617F status, when compared to the control group. The median values of activated CECs were markedly higher in PV patients with WBC >8.7 (x10(9)/l). Significantly higher VEGF plasma levels were found in ET patients and a similar trend was seen in PV patients in relation to healthy volunteers. The plasma levels of sVEGFR-1 were significantly higher, and PlGF levels markedly lower, in the ET and PV group than in controls. Our study also demonstrated markedly increased levels of D-dimer and TAT complexes in the patient groups. In conclusion, we found that angiogenesis, as measured by CEC numbers, is increased in ET and PV patients regardless of JAK2-V617F mutational status. Our results demonstrated that angiogenic cytokines interact with known thrombotic risk factors. We confirmed the coagulation activation in ET and PV patients but found no differences in levels of coagulation activation markers in relation to JAK2-V617F mutational status.
authors.affiliation: Department of Hematology, Copernicus Memorial Hospital, Medical University of Lodz, Ciolkowskiego 2, 93-510, Lodz, Poland. jtrel2001@yahoo.com
authors.forename: Jacek
authors.initials: J
authors.lastname: Treliński
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wierzbowska
authors.forename: Anna
authors.initials: A
authors.lastname: Krawczyńska
authors.forename: Agata
authors.initials: A
authors.lastname: Sakowicz
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pietrucha
authors.forename: Piotr
authors.initials: P
authors.lastname: Smolewski
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Chojnowski
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000097:blood; D000072483:Placenta Growth Factor; D011087:Polycythemia Vera / Q000097:blood* / Q000235:genetics; D011257:Pregnancy Proteins / Q000097:blood; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood
chemical_list: C000608036:PGF protein, human; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D053614:Janus Kinase 2
references.citation: Leuk Res. 2009 Jan;33(1):67-73
references.pmid: 18632151
references.citation: Br J Haematol. 2009 Jul;146(2):150-7
references.pmid: 19466975
references.citation: J Biol Chem. 1994 Oct 14;269(41):25646-54
references.pmid: 7929268
references.citation: J Clin Invest. 2000 Jan;105(1):71-7
references.pmid: 10619863
references.citation: Eur J Haematol. 2005 Dec;75(6):492-7
references.pmid: 16313261
references.citation: Haematologica. 2009 Jul;94(7):911-8
references.pmid: 19508974
references.citation: Exp Hematol. 2009 Sep;37(9):1016-21
references.pmid: 19559071
references.citation: Pol Merkur Lekarski. 2006 Jun;20(120):717-20
references.pmid: 17007278
references.citation: Br J Haematol. 2008 Jan;140(2):162-8
references.pmid: 18028479
references.citation: J Mol Med (Berl). 1999 Jul;77(7):527-43
references.pmid: 10494799
references.citation: J Thromb Haemost. 2007 Apr;5(4):708-14
references.pmid: 17263783
references.citation: Haematologica. 2006 Feb;91(2):169-75
references.pmid: 16461300
references.citation: Blood. 2002 Jun 1;99(11):4131-7
references.pmid: 12010817
references.citation: Nat Med. 2001 May;7(5):575-83
references.pmid: 11329059
references.citation: Blood. 2005 Apr 15;105(8):3286-94
references.pmid: 15618473
references.citation: Leukemia. 2007 Sep;21(9):1952-9
references.pmid: 17625606
references.citation: Hematology. 2007 Dec;12(6):481-6
references.pmid: 17852434
references.citation: Haematologica. 2002 Jul;87(7):774-5
references.pmid: 12091131
references.citation: Blood. 2007 Mar 15;109(6):2310-3
references.pmid: 17110452
references.citation: Blood. 2000 Dec 15;96(13):4261-6
references.pmid: 11110700
references.citation: Lancet. 2005 Mar 19-25;365(9464):1054-61
references.pmid: 15781101
references.citation: Br J Cancer. 1998 Mar;77(6):956-64
references.pmid: 9528841
references.citation: Blood. 2001 Jun 1;97(11):3658-61
references.pmid: 11369666
references.citation: Leukemia. 2008 Jan;22(1):14-22
references.pmid: 17882280
references.citation: Leuk Lymphoma. 2009 Feb;50(2):247-53
references.pmid: 19235016
references.citation: Am J Hematol. 2002 Mar;69(3):159-63
references.pmid: 11891801
references.citation: Br J Haematol. 2005 Feb;128(3):275-90
references.pmid: 15667529
references.citation: Cancer Res. 2001 Jun 1;61(11):4341-4
references.pmid: 11389057
references.citation: Blood. 2006 Jul 15;108(2):452-9
references.pmid: 16543470
references.citation: Thromb Res. 2009 Sep;124(4):409-17
references.pmid: 19299003
references.citation: Leuk Lymphoma. 2005 Sep;46(9):1345-51
references.pmid: 16109613
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10857-62
references.pmid: 11553814
references.citation: Mayo Clin Proc. 2006 Feb;81(2):159-66
references.pmid: 16471068
references.citation: Ann Oncol. 2004 Jan;15(1):139-45
references.pmid: 14679134
references.citation: J Thromb Haemost. 2007 Aug;5(8):1679-85
references.pmid: 17596137
references.citation: Hematol Oncol. 2008 Dec;26(4):235-9
references.pmid: 18504767
references.citation: Blood. 2007 Aug 1;110(3):840-6
references.pmid: 17379742
references.citation: Leuk Lymphoma. 2009 Jan;50(1):62-7
references.pmid: 19125384
references.citation: Nat Med. 2003 Jun;9(6):669-76
references.pmid: 12778165
references.citation: Blood Coagul Fibrinolysis. 2009 Dec;20(8):646-51
references.pmid: 19741509
references.citation: Hematology. 2000;4(5):397-402
references.pmid: 11399581
references.citation: Arterioscler Thromb Vasc Biol. 1999 Jul;19(7):1757-60
references.pmid: 10397695
references.citation: Pathol Oncol Res. 2003;9(3):170-3
references.pmid: 14530810
references.citation: Exp Hematol. 2005 May;33(5):523-30
references.pmid: 15850829
references.citation: Cancer Res. 1999 Feb 1;59(3):728-33
references.pmid: 9973224