@Article{,
AUTHOR = {Halina Urbañska-Rys´, Agnieszka Wierzbowska, Tadeusz Robak},
TITLE = {Circulating angiogenic cytokines in multiple myeloma and related disorders},
JOURNAL = {European Cytokine Network},
VOLUME = {14},
YEAR = {2003},
NUMBER = {1},
PAGES = {40--51},
URL = {http://www.techscience.com/ECN/v14n1/66551},
ISSN = {1952-4005},
ABSTRACT = {We investigated the serum concentrations of selected angiogenic cytokines including: vascular
endothelial growth factor (VEGF), hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGF-β1)
and basic fibroblast growth factor (bFGF) in 162 patients with multiple myeloma (MM), 5 patients with
Waldenström’s macroglobulinaemia (WM), and 31 healthy controls. Among the MM patients there were 2 cases
of primary plasma cell leukemia (PCL) and one case of extramedullary plasmacytoma. The levels of measured
cytokines were correlated with the phase and stage of the disease as well as the most important clinical and
laboratory parameters associated with disease activity (haemoglobin, creatinine, albumins, calcium,
M-component, CRP, β2m, LDH and bone involvement). We have found correlations between serum levels of
angiogenic cytokines and some parameters depicting the disease activity and advancement. The serum level of
VEGF in MM patients (median 244.5 pg/mL) correlated with serum concentrations of beta-2-microglobulin (β2m)
greater than 2.5 mg/L (p = 0.0005) and abnormal values of lactate dehydrogenase (> 425 U/L, median
– 329.0 pg/mL and < 210 U/L, median – 426.6 pg/mL, p = 0.004 and p = 0.04 respectively). MM patients in stage
III had higher serum levels of HGF (median – 1 411.3 pg/mL) than those in stage I (median – 1 219 pg/mL)
(p = 0.01) according to Durie and Salmon staging, and those in phase I (at diagnosis) (median 1 555.6 pg/mL) and
phase III (in progression) (median 1 309.7 pg/mL) had higher levels than those in phase II (plateau phase) (median
1 047.9 pg/mL) (p = 0.002 and p = 0.02 respectively). Significantly elevated values of HGF were found in MM
patients with anaemia (median – 1 962.0 pg/mL) and hypercalcaemia (median – 2 085.6 pg/mL) (p = 0.00001 and
0.04 respectively). TGF-β1 (median – 33.9 ng/mL) correlated positively with high b2m values (> 2.5 mg/L)
(p = 0.04) and was significantly higher in phase I (median – 40.1 ng/mL) than in phase II (median – 30.9 ng/mL)
(p = 0.03) of the disease. The concentration of bFGF was significantly higher in stage III of MM
(median – 3.1 pg/mL) than in stage I (median – 1.2 pg/mL) (p = 0.04). We found that the survival probability was
statistically higher for newly diagnosed MM patients with a concentration of VEGF lower than the median value
for this cytokine. The concentrations of the cytokines analyzed in patients with Waldenström’s macroglobuli-naemia
(WM), primary plasma cell leukaemia (PCL) and non-secretory (NS) myeloma were not distinguishable
from those found in MM patients. We also studied the relationship between the levels of cytokines analyzed and
found positive correlations between bFGF and TGF-β1 (q = 0.183, p < 0.02), as well as VEGF and TGF-β1
(q = 0.537, p < 0.001) and VEGF and bFGF (q = 0.197, p < 0.02). In conclusion, our data indicate a strong
relationship between angiogenic cytokine serum levels and clinical course as well as selected laboratory
parameters of patients with MM.},
DOI = {}
}