Plasma levels of soluble endoglin have prognostic significance in patients with chronic lymphocytic leukemia

Czech version

Authors: L. Smolej ¹; C. Andrýs ²; D. Belada ¹; M. Hrudková ¹; J. Krejsek ²; J. Malý ¹
Authors‘ workplace: II. interní klinika, oddělení klinické hematologie1 a Ústav klinické imunologie a alergologie2, Fakultní nemocnice a Lékařská fakulta Univerzity Karlovy v Hradci Králové.
Published in: Transfuze Hematol. dnes,14, 2008, No. 1, p. 24-27.
Category: Comprehensive Reports, Original Papers, Case Reports

Overview

Angiogenesis has been recently extensively studied in a wide spectrum of hematological malignancies. Endoglin (CD105), member of transforming growth factor beta (TGF-beta) receptor family, modulates cellular responses to TGF-beta and is essential for angiogenic processes. Elevated circulating levels of soluble endoglin (sCD105) have been reported in patients with various solid tumors and several hematological malignancies. In the present study, we measured peripheral blood plasma concentrations of sCD105 using enzyme-linked immunosorbent assay in 79 patients with chronic lymphocytic leukemia and 69 healthy donors. We found a statistically significant increase in sCD105 concentrations in patients with CLL compared to controls (mean ± standard deviation: 6.8 ± 2.1 vs. 4.6 ± 1.5 ng/ml, 95% confidence interval of mean: 6.4-7.3 vs. 4.2-4.9 ng/ml, p<0.0001). Patients with progressive CLL had higher sCD105 than patients with indolent disease (p=0.0016). Soluble endoglin increased significantly with Rai stage (Rai 0 vs. I-II vs. III-IV, p=0.009 and p=0.04). Progression-free survival was significantly shorter in patients with sCD105 levels above mean (median 15 months vs. not reached, p=0.0045). In conclusion, our data suggest that endoglin may play a significant role in CLL biology and progression; its quantification could contribute to better understanding of angiogenic processes and refine prognostication of individual patients in this disease.

Key words:
endoglin, CD105, angiogenesis, CLL, prognosis

Sources

1. Folkman J. Angiogenesis in cancer, vascular, rheumatoid, and other disease. Nat Med 1995; 1: 27–31.

2. Rajkumar SV, Mesa, RA, Tefferi, A. A review od angiogenesis and anti-angiogenic therapy in hematological malignancies. J Hematother Stem Cell Res 2001; 11: 33–47.

3. Pour L, Hájek R, Büchler T, Maisnar V, Smolej L: Angiogeneze a antiangiogenní léčba u nádorů. Vnitř Lék 2004; 12: 930–8.

4. Hussong JW, Rodgers GM, Shami PJ. Evidence of increased angiogenesis in patients with acute myeloid leukemia. Blood 2000; 95: 309.

5. Aguayo A, Kantarjian H, Manshouri T, Gidel C, Estey E, Thomas D, Koller C, Estrov Z, O’Brien S, Keating M, Freireich E, Albitar M: Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood 2000; 96: 2240–5

6. Rajkumar SV, Leong T, Roche PC, Fonseca R, Dispenzieri A, Lacy MQ, Lust JA, Witzig TE, Kyle RA, Gertz MA, Greipp PR: Prognostic value of bone marrow angiogenesis in multiple myeloma. Clin Cancer Res 2000; 6: 3111–3116

7. Molica S, Vacca A, Ribatti D, Cuneo A, Cavazzini F, Levato D, Vitelli G, Tucci L, Roccaro AM, Dammacco F: Prognostic value of enhanced bone marrow angiogenesis in early B-cell chronic lymphocytic leukemia. Blood 2002; 100: 3344–51.

8. Smolej L, Žák P, Belada D, Malý J. Diagnostika a léčba chronické lymfocytární leukemie. Lék Zpr LF UK Hradec Králové 2007;52(1): 23–34.

9. Papajík T, Jarošová M, Pikalová Z, Indrák K. Chronická B-lymfocytární leukemie Část II: Diagnostická kritéria a význam stanovení individuální prognózy nemocného. Trans Hemat dnes 2006; 3: 132–9.

10. Kašparová P, Smolej L. Angiogeneze v kostní dřeni u pacientů s chronickou lymfocytární leukemií. Čes-slov Patol 2007; 43(2): 50–58.

11. Cheifetz S, Bellon T, Cales C, Vera S, Bernabeu C, Massague J, Letarte M. Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. J Biol Chem. 1992; 267(27): 19027–30.

12. Duff SE, Li C, Garland JM, Kumar S: CD105 is important for angiogenesis: evidence and potential applications. FASEB J 2003; 17: 984–92.

13. Fonsatti E, Altomonte M, Nicotra MR, Natali PG, Maio M. Endoglin (CD105): a powerful therapeutic target on tumor-associated angiogenetic blood vessels. Oncogene 2003; 22: 6557–63.

14. Arthur HM, Ure J, Smith AJ, Renforth G, Wilson DI, Torsney E, Charlton R, Parums DV, Jowett T, Marchuk DA, Burn J, Diamond AG. Endoglin, an ancillary TGF-beta receptor, is required for extraembryonic angiogenesis and plays a key role in heart development. Dev Biol 2000; 217: 42–53.

15. Lebrin F, Goumans MJ, Jonker L, Carvalho RL, Valdimarsdottir G, Thorikay M, Mummery C, Arthur HM, Dijke Pt P. Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction. EMBO J 2004; 1–11.

16. Miller DW, Graulich W, Karges B, Stahl S, Ernst M, Ramaswamy A, Sedlacek HH, Muller R, Adamkiewicz J. Elevated expression of endoglin, a component of the TGF-beta-receptor complex, correlates with proliferation of tumor endothelial cells. Int J Cancer 1999; 81: 568–72.

17. Li C, Guo B, Wilson PB, Stewart A, Byrne G, Bundred N, Kumar S. Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer. Int J Cancer 2000; 89:122–6.

18. Li C, Gardy R, Seon BK, Duff SE, Abdalla S, Renehan A, O’Dwyer ST, Haboubi N, Kumar S. Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis. Br J Cancer 2003; 88: 1424–31.

19. Takahashi N, Kawanishi-Tabata R, Haba A, Tabata M, Haruta Y, Tsai H, Seon BK. Association of serum endoglin with metastasis in patients with colorectal, breast, and other solid tumors, and suppressive effect of chemotherapy on the serum endoglin. Clin Cancer Res 2001; 7: 524–32.

20. Yagmur E, Rizk M, Stanzel S, Hellerbrand C, Lammert F, Trautwein C, Wasmuth HE, Gressner AM. Elevation of endoglin (CD105) concentrations in serum of patients with liver cirrhosis and carcinoma. Eur J Gastroenterol Hepatol. 2007; 19(9): 755–61.

21. Calabro L, Fonsatti E, Bellomo G, Alonci A, Colizzi F, Sigalotti L, Altomonte M, Musolino C, Maio M. Differential levels of soluble endoglin (CD105) in myeloid malignancies. J Cell Physiol 2003; 194: 171–5.

22. Catchpoole D, Lail A, Guo D, Chen QR, Khan J. Gene expression profiles that segregate patients with childhood acute lymphoblastic leukaemia: An independent validation study identifies that endoglin associates with patient outcome. Leuk Res 2007; 31(12): 1741–7.

23. Smolej L., Andrýs C., Belada D., Maisnar V., Žák P., Široký O., Malý J. Plazmatické koncentrace solubilního endoglinu u nemocných s lymfoidními malignitami. Trans Hemat dnes 2006; 12(1): 37–39.

24. Cheson BD, Bennett JM, Grever M, Kay NE, Keating MJ, O’Brien S, Rai KR. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: Revised guidelines for diagnosis and treatment. Blood 1996; 87: 4990–7.

Labels

Haematology Internal medicine Clinical oncology

Prenatal and postnatal immunohematology

RNA vaccine – clinical studies

Veno-occlusive disease (Sinusoidal obstruction syndrome)

Article was published in

Transfusion and Haematology Today

2008 Issue 1