Serum levels of soluble adhesion molecules in newly diagnosed acute myeloid leukemia and in complete remission suggest endothelial cell activation by myeloblasts.
OBJECTIVE
Despite high-dose multi-agent chemotherapy and allogeneic stem cell transplantation, the relapse rate of acute myeloid leukemia (AML) is high. Further, the disease is highly resistent to drugs. We speculated that deeper understanding of AML-endothelial cell interactions might provide new targets for selective modulation of the AML microenvironment and form the basis for novel treatment approaches. In this study, we evaluated levels of endothelium derived soluble adhesion molecules in active disease and in complete remission (CR) and their relationship with inflammatory cytokines.


METHODS
Baseline serum levels of 25 cytokines and 5 soluble adhesion molecules were measured in 84 AML patients using biochip array technology. CR samples were evaluated in 44 patients of this cohort. The control group consisted of 15 healthy blood donors.


RESULTS
All analytes were independent of age or disease origin. Some correlations were restricted to active AML, some were ubiquitous and some were found in remission. In active disease, E-selectin (E-SEL) and VCAM-1 correlated with leukocyte count, E-SEL correlated with P-selectin (P-SEL). Platelet count related to IL-7, EGF and VEGF but not to P-SEL. In CR, P-SEL correlated with platelet count and EGF but not with E-SEL. There was no relationship of P-SEL and E-SEL in the control group.


CONCLUSIONS
Leukemic activity is associated with a different pattern of soluble adhesion molecule levels. Both E-SEL and P-SEL may be derived from endothelial cells. Their levels correlated in active disease. E-SEL correlated with leukocyte count. In CR, P-SEL physiologically correlated with platelet count. The correlation with E-SEL was insignificant and absent in the control group. Our data suggest activation of endothelial cells in the presence of myeloblasts.
Department of Military Internal Medicine and Military Hygiene, University of Defence, Faculty of Military Health Sciences (FMHS), Hradec Kralove, Czech Republic.|4th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove, Czech Republic.
Tomas
T
Kupsa
Department of Informatics and Quantitative Methods, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic.
Jan
J
Vanek
4th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove, Czech Republic.|4th Department of Internal Medicine - Hematology, Faculty of Medicine, Charles University in Prague, Hradec Kralove, Czech Republic.
Zak
Z
Pavel
Department of Military Internal Medicine and Military Hygiene, University of Defence, Faculty of Military Health Sciences (FMHS), Hradec Kralove, Czech Republic.|4th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove, Czech Republic.
Ladislav
L
Jebavy
Department of Military Internal Medicine and Military Hygiene, University of Defence, Faculty of Military Health Sciences (FMHS), Hradec Kralove, Czech Republic.|4th Department of Internal Medicine - Hematology, University Hospital Hradec Kralove, Czech Republic.
Jan M
JM
Horacek
D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D042381:Granulocyte Precursor Cells / Q000502:physiology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015815:Cell Adhesion Molecules; D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; D002097:C-Reactive Protein
acute myeloid leukemia; adhesion molecules; complete remission; cytokines; endothelial cell