| Abstract |
Background: Multiple myeloma is a malignant plasma cell diseaes, being located in bone
marrow. Malignant cells interact with bone marrow microenvironment, modifying it.
Angiogenesis represents the formation of new blood vessels from pre-existing ones, is
dependent on those interactions, and finally is implicated in the development of tumor
by multiple manners. Angiogenesis process has been studied in both benign and
malignant diseases included multiple myeloma, achieving the development of antiangiogenic
therapies, even in myeloma, with satisfying results. Despite the progress in the
understanding of myeloma pathophysiology, the disease remains incurable. Therefore,
the investigation of implicated mechanisms in the biology of myeloma evolution is
nessecary.
Aim of the study: The aim of the study was to investigate the role of ELR CXC+
chemokines and mast cells in angiogenic activity of multiple myeloma. Circulating levels
of those chemokines in the peripheral blood, as well mast cells’ location in bone marrow
were studied. Furthermore, their relationship with bone marrow angiogenic process was
also studied.
Patients and methods: Sixty-three myeloma patients were studied during diagnosis.
Moreover, 30 of them achieving remission after therapy as well 30 healthy controls were
also studied. This was a study in 2 phases. Initially, ELR+ CXC chemokines (GRO-α,
ENA-78 and ΙL-8) were measured in peripheral blood, along with the estimation of bone
marrow angiogenic activity, both directly, estimating bone marrow microvascular density
(MVD) and indirectly, measuring circulating levels of known angiogenic cytokines, such
as HGF, VEGF, TNF-α, angiogenin and PDGF-AB. In the next phase, bone marrow
mast cell density (MCD) was estimated, along with the estimation of bone marrow
angiogenic activity, both directly, estimating bone marrow microvascular density (MVD)
and indirectly, measuring circulating levels of known angiogenic cytokines, such as
VEGF, bFGF, TNF-α, as well ELR+ CXC chemokines.
Results: All measured variables were significantly increased in multiple myeloma patients
compared to healthy population. Furthermore, they were all increasing in parallel with
disease activity, with the exception of ENA-78. Similarly, all variables decreased after
effective treatmen, with the exceptions of ENA-78 and GRO-α, where no difference was
found. Significant positive correlations were found between GRO-α with HGF, VEGF,
TNF-α, MVD and MCD. Significant positive correlations were also noted between
ΕΝΑ-78 with VEGF, TNF-α and MCD but not with MVD. IL-8 also correlated with
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TNF-α, PDGF-AB, angiogenin and MCD, but also not with MVD. Finally, MCD
correlated with MVD and all angiogenic cytokines as well.
Conclusions: Circulating levels of ELR+ CXC chemokines (IL-8, GRO-α and ΕΝΑ-
78), as well bone marrow MCD are elevated in multiple myeloma patients, are dependent
on disease stage and decrease after effective therapy. Their correlations with the
angiogenic process suggest their participation in multiple myeloma angoiogenesis.
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Διερεύνηση του ρόλου των μαστοκυττάρων και CXC ELR motif (ELR+)χυμοκινών στην αγγειογένεση του πολλαπλού μυελώματος
