Differential levels of soluble angiopoietin‐2 and Tie‐2 in patients with haematological malignancies

Abstract

The system involving angiopoietin-2 (Ang-2) and its receptor, Tie-2, appears to play an important role not only in tumor angiogenesis, but also in the biology of haematological and non-haematological malignancies. In the present study we evaluated the serum levels of soluble Ang-2 (sAng-2) and soluble Tie-2 (sTie-2) in patients with haematological malignancies. Measurements were carried out in 15 patients with chronic myeloid leukaemia (CML), 25 with essential thrombocythemia (ET), 24 with multiple myeloma (MM) and six with monoclonal gammopathy of undetermined significance (MGUS). In addition, we correlated the levels of angiopoietins with known prognostic factors. sAng-2 and sTie-2 were quantified with enzyme-linked immunosorbent assay (ELISA). In patients with CML and MM the levels of sAng-2 were significantly higher (1686.53 +/- 936.41 pg/mL and 1917.82 +/- 1427 pg/mL, respectively) than in controls (n = 15; 996.096 +/- 414.65 pg/mL) (P < 0.01). In patients with MM sAng-2 levels were significantly increased with increasing stage of disease, from stage I to stage III (P < 0.03) and presented a trend of correlation with Beta2-microglobulin levels (r = 0.317) and grade of bone involvement. Furthermore, the levels of sAng-2 determined after 6 months of chemotherapy in CML patients were significantly lower than at diagnosis in the patients who achieved haematological remission. Circulating sTie-2 levels were increased in patients with ET (17.5 +/- 9.2 vs 9 +/- 3.5 ng/mL; P < 0.01) and in those with CML (16.29 +/- 8.7 ng/mL; P < 0.04). In conclusion, abnormal levels of sAng-2 and sTie-2 are present in some haematological malignancies. These markers may play a role in the pathophysiology of these conditions and their progression.

Prognostic value of soluble angiopoietin-2 and soluble Tie-2 in Egyptian patients with acute myeloid leukemia

“…Furthermore, it is conceivable that Ang-2 could also be released by the endothelium of the normal vasculature upon dysregulated stimulation by leukemic blasts [19]. Our findings are in line with a recent observation of elevated Ang-2 and Tie-2 levels in patients with chronic myeloid leukemia (CML) and multiple myeloma [14]. It was found that blood levels of sAng-2 and sTie-2 were strongly associated with the extent of BM infiltration, TLC and LDH, providing indirect evidence that the leukemic blasts themselves at least significantly contributed to the plasma levels of the tested angiogenic factors [19].…”

“…The overall survival is significantly shorter in AML patients with plasma Ang-2 2500 pg/ml than in those with levels <2500 pg/ml T E22 <=8 >8 <=8-censored >8-censored documented that the tumor cells themselves emit proteins that stimulate neoangiogenesis and this process is correlated with the diffusion of metastases [22]. Elevated levels of circulating Ang-2 have been linked with angiogenesis in malignancies such as angiosarcoma [23], breast cancer [24], and multiple myeloma and CML [14] . In analogy, high levels of Ang-2 in AML may contribute to angiogenesis in the BM in the presence of mitogenic mediators, thereby facilitating leukemic blast proliferation and disease progression.…”

“…The role of this complex system has been extensively examined in the neovascularization of a wide variety of tumors, and many reports have documented a correlation between Ang expression and clinical features or prognosis [14]. Loges et al [15] reported that BM neoangiogenesis plays an important pathogenic and possibly prognostic role in AML.…”

Circulating angiopoietin-2 is a strong prognostic factor in acute myeloid leukemia

“…25 However, no data are so far available on blood levels of angiopoietins and their soluble receptor Tie2 (sTie2) in AML. Furthermore, while elevated blood levels of Ang-2 have been detected in patients with angiosarcoma, 26 breast cancer, 27 multiple myeloma and chronic myeloid leukemia, 28 to the best of our knowledge, there are no studies available on the prognostic value of soluble angiopoietins in any type of cancer.…”

Angiopoietin-2 expression in B-cell chronic lymphocytic leukemia: association with clinical outcome and immunoglobulin heavy-chain mutational status

“…Abnormal serum levels of angiopoietin-2 (Ang-2) were found in several hematological malignancies. 3,4 The report of Hü ttmann et al, 5 recently published in Leukemia, described an increase of Ang-2 plasma levels in the ZAP-70 þ CD38 þ as compared to the ZAP-70 À CD38 À CLL patients. Moreover, Ang-2 plasma levels detected in Binet B and C patients exceeded those of Binet stage A cases, suggesting a correlation between Ang-2 secretion and CLL progression.…”