Elevated serum angiogenin in multiple myeloma

Alexandrakis, Michael G.; Passam, Freda; Sfiridaki, Aekaterini; Kyriakou, Despina; Petreli, Elisa; Roussou, Paraskevi

doi:10.1038/sj.thj.6200331

Cited by 13 publications

(12 citation statements)

References 9 publications

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“…Increased circulating levels of VEGF and of angiogenin have been previously described in patients with MM [20][21][22] and our results confirm these observations. The effect of circulating VEGF on survival of myeloma patients who received CC was previously reported but the results were conflicting.…”

Section: Discussionsupporting

confidence: 82%

Circulating angiopoietin‐1 to angiopoietin‐2 ratio is an independent prognostic factor for survival in newly diagnosed patients with multiple myeloma who received therapy with novel antimyeloma agents

Terpos

Anargyrou

Katodritou

et al. 2011

Intl Journal of Cancer

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The circulating levels of several angiogenic cytokines [angiopoietin‐1 (Ang‐1), angiopoietin‐2 (Ang‐2), vascular endothelial growth factor (VEGF), angiogenin and basic fibroblast growth factor (bFGF)] were evaluated in 174 consecutive patients with newly diagnosed, symptomatic, multiple myeloma (MM). Circulating levels of Ang‐1/Ang‐2 were reduced in myeloma patients compared to controls, whereas VEGF and angiogenin levels were increased. Reduced angiopoietin‐1/angiopoietin‐2 ratio correlated with advanced disease features including international staging system (ISS)‐3 stage, renal impairment and extensive bone disease. Based on immunohistochemical results in 20 patients (10 with the higher and 10 with the lower values of circulating angiopoietin‐2) we found that angiopoietin‐2 is expressed by myeloma cells and correlates with increased microvessel density in subsets of patients. Furthermore, Ang‐1/Ang‐2 ratio correlated with survival. Patients with circulating Ang‐1/Ang‐2 below or equal to the median value (6.03) had a median survival of 26.3 months compared to 53 months of all others (p = 0.002). Interestingly, this was mainly observed in patients who received first‐line therapy with novel agent‐based regimens (65% of our patients). Furthermore, a subset of ISS‐3 patients with serum Ang‐1/Ang‐2 above the median value had favourable prognosis (median survival: 45 months versus 17 months of all others; p = 0.0001). The multivariate analysis revealed that low Ang‐1/Ang‐2 ratio could independently predict for inferior survival in our cohort of patients (relative risk (RR) 2.07, 95% CI 1.50–2.42; p < 0.001). These results highlight the role of angiopoietins pathway in the biology of MM and reveal novel targets for the development of antimyeloma agents.

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Section: Discussionsupporting

confidence: 82%

Circulating angiopoietin‐1 to angiopoietin‐2 ratio is an independent prognostic factor for survival in newly diagnosed patients with multiple myeloma who received therapy with novel antimyeloma agents

Terpos

Anargyrou

Katodritou

et al. 2011

Intl Journal of Cancer

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“…Angiogenin has also been implicated as a mitogen for vascular endothelial cells [18]. Angiogenin activity may be important for the maintenance and support of tumour growth, and in MM patients, its serum levels correlate with myeloma tumour load [19]. We found that angiogenin levels decreased following bortezomib treatment.…”

Section: Introductionsupporting

confidence: 51%

Anti-Angiogenic Effect of Bortezomib in Patients with Multiple Myeloma

Politou

Naresh²,

Terpos³

et al. 2005

Acta Haematol

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“…Increased levels of angiogenin have been described in solid tumours and myelodysplastic syndromes, especially in the subtypes with a high-risk for leukaemic transformation [31]. Serum levels of angiogenin are elevated in newly diagnosed MM patients [27,32], while in relapsed/ refractory MM angiogenin levels were higher in patients with advanced stage disease [29]. These observations suggest that angiogenin has a distinct role in MM angiogenesis that needs further investigation.…”

mentioning

confidence: 92%

Novel anti-myeloma agents and angiogenesis

Anargyrou

Dimopoulos

Sezer

et al. 2008

Leukemia & Lymphoma

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During the last decade several novel agents have been used in the management of patients with multiple myeloma. Immunomodulatory drugs and proteasome inhibitors exert their efficacy both directly by inducing apoptosis of myeloma cells and indirectly through the interruption of the interactions between myeloma and stromal cells in the bone marrow (BM) microenvironment. These interactions are crucial for myeloma cell growth and survival. The adherence of myeloma cells to BM stromal cells leads to the overproduction of several cytokines with angiogenic properties that enhance the survival and growth of myeloma cells through paracrine and autocrine loops. The correlation of these molecules with clinical features and survival of myeloma patients supports the importance of angiogenesis in the pathogenesis of the disease and reveals these cytokines as suitable targets for the development of novel anti-myeloma therapies. This review summarises all available preclinical and clinical data for the effect of novel agents that are used in myeloma therapy, such as thalidomide, lenalidomide, bortezomib and VEGF inhibitors, on angiogenesis, which is at least partially responsible for their remarkable anti-myeloma efficacy.

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Elevated serum angiogenin in multiple myeloma

Cited by 13 publications

References 9 publications

Circulating angiopoietin‐1 to angiopoietin‐2 ratio is an independent prognostic factor for survival in newly diagnosed patients with multiple myeloma who received therapy with novel antimyeloma agents

Circulating angiopoietin‐1 to angiopoietin‐2 ratio is an independent prognostic factor for survival in newly diagnosed patients with multiple myeloma who received therapy with novel antimyeloma agents

Anti-Angiogenic Effect of Bortezomib in Patients with Multiple Myeloma

Novel anti-myeloma agents and angiogenesis

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