| Abstract |
Existing data: Multiple myeloma (MM) is a plasma cell malignancy, locating in bone marrow environment. In order to survive and subsequently to expand, myeloma plasma cells interact with bone marrow’s elements, activating various mechanisms that aim, directly (plasma cell proliferation) and indirectly (induction of angiogenesis in order to carry oxygen and nutrients, creation of bone disease in order to provide space for the expansion of the disease) the evolution of the disease. It is of interest that those interactions usually operate in multiple levels, causing significant alteration of bone marrow microenvironment that favors the development of the myeloma clone. An important characteristic of the altered environment is the pathologic expression of various versatile cytokines.
Aim of the study: The research of the role of various molecules in angiogenesis and bone disease in MM. We measured the peripheral expression of various molecules and examined the relation between this expression, both with bone marrow angiogenic activity and bone disease.
Patients and methods: We studied 78 MM patients in diagnosis, 35 of them in remission after treatment and 30 healthy controls. The study was performed in 4 independent stages: in the first stage we studied the relation between known angiogenic factors (MMP-9, VEGF, HGF) with indices of bone disease (grade of bone disease and indices of bone metabolism: serum PICP and urine Ntx) and burden of disease (B2M, albumin and clinical stage). In the second stage we studied serum levels of IL-6 and MMP-9 in combination with indices of bone disease ( Nxt, F-Pyd and F-Dpd in urine, grade of bone disease) and disease activity (stage and infiltartion), in order to estimate if they are useful prognostic indices for the bone disease. In the third stage we studied the relation of RANKL and osteoprotegerin with known markers of angiogenesis (HGF, VEGF), disease activity (IL-6, LDH, B2M, CRP, stage, before and after effective treatment) and bone disease (grade of bone disease). In the fourth stage, we measured the levels of circulating osteopontin and VEGF, the microvasular density of bone marrow (markers of angiogenesis), urine Ntx and grade of bone disease (markers of bone disease), bone marrow infiltration and clinical stage (markers of myeloma burden), both in diagnosis and after effective treatment.
Results: ΜΜΡ-9 was correlated to clinical stage, bone disease grade, angiogenic cytokines VEGF and HGF, IL-6 and indices of bone metabolism (positively withNTx, F-Pyd, FDpd and negatively with PICP). RANKL but not OPG neither the rate RANKL/OPG, was increased in MM patients. RANK and the rate, but not OPG, increased in parallel with disease stage and grade of bone disease, wheraes all values failed in the plateau phase. RANKL correlated with markers of angiogenesis and disease activity, wheraes the rate RANKL/OPG additionaly correlated with OPG. Finally, OPN, although not significantly elevated in MM patients, correlated with grade of bone disease, stage and burden of the disease, failed in the plateau phase, whereas values >100ng/ml were suggestive of progressed disesase.
Conclusions: The circulating levels of the above molecules seem to participate in the process of angiogenesis and bone distruction. Measuring their levels might add in the assessment of bone disease, whereas osteopontin has prognostic value. That information might help in the clinical practice, since they could detect high risk patients, or be used as additional markers of response to treatment or even relapse.
|
Collections
