Skip to main content

Advertisement

SpringerLink
Log in

Circulating endothelial cells in patients with chronic lymphocytic leukemia

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Angiogenesis is increased in B-cell chronic lymphocytic leukemia (B-CLL). We wanted to quantify and characterize the circulating endothelial cells (CECs) in patients with B-CLL and correlate with plasma angiogenesis-related factors. Using a four-color flow cytometry, we prospectively analyzed the CEC in the whole blood of 20 healthy controls and 20 patients with B-CLL. We quantified (CD45−/CD31+/CD146+) and characterized the CECs according to whether they were apoptotic (annexin stain) or activated (CD106+). We also measured plasma levels of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), and thrombospondin-1 (TSP-1). Most patients (90%) had Rai stages 0–2 at the time of diagnosis. As a group, B-CLL patients had higher number of CECs (median of 26.5 cells/ml) compared (P = 0.04) to healthy controls (18.5 cells/ml). However, only four (20%) patients had elevated CEC counts, defined as ≥2 SD of the control mean (≥53 cells/ml). The proportions of apoptotic (P = 0.83) and activated (P = 0.12) CECs were similar in both groups. B-CLL patients had higher FGF-2 (P < 0.001), lower TSP-1 (P = 0.004), and similar VEGF (P = 0.27) plasma levels. The number of CECs was not associated with Rai stage, absolute lymphocyte count, or levels of angiogenesis-related factors. CECs are increased in only a small fraction of B-CLL patients in our cohort with low rates of apoptosis and activation. While no correlation was found between CECs and clinical features, more studies in a larger patient sample size and advanced disease are necessary.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kini AR, Kay NE, Peterson LC (2000) Increased bone marrow angiogenesis in B cell chronic lymphocytic leukemia. Leukemia 14:1414–1418

    Article  PubMed  CAS  Google Scholar 

  2. Chen H, Treweeke AT, West DC, Till KJ, Cawley JC, Zuzel M et al (2000) In vitro and in vivo production of vascular endothelial growth factor by chronic lymphocytic leukemia cells. Blood 96:3181–3187

    PubMed  CAS  Google Scholar 

  3. Molica S, Vacca A, Ribatti D, Cuneo A, Cavazzini F, Levato D et al (2002) Prognostic value of enhanced bone marrow angiogenesis in early B-cell chronic lymphocytic leukemia. Blood 100:3344–3351

    Article  PubMed  CAS  Google Scholar 

  4. Bairey O, Boycov O, Kaganovsky E, Zimra Y, Shaklai M, Rabizadeh E (2004) All three receptors for vascular endothelial growth factor (VEGF) are expressed on B-chronic lymphocytic leukemia (CLL) cells. Leuk Res 28:243–248

    Article  PubMed  CAS  Google Scholar 

  5. Blann AD, Woywodt A, Bertolini F, Bull TM, Buyon JP, Clancy RM et al (2005) Circulating endothelial cells. Biomarker of vascular disease. Thromb Haemost 93:228–235

    CAS  Google Scholar 

  6. Bertolini F, Shaked Y, Mancuso P, Kerbel RS (2006) The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer 11:835–845

    Article  Google Scholar 

  7. Mancuso P, Burlini A, Pruneri G, Goldhirsch A, Martinelli G, Bertolini F (2001) Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood 97:3658–3661

    Article  PubMed  CAS  Google Scholar 

  8. Zhang H, Vakil V, Braunstein M, Smith EL, Maroney J, Chen L et al (2005) Circulating endothelial progenitor cells in multiple myeloma: implications and significance. Blood 105:3286–3294

    Article  PubMed  CAS  Google Scholar 

  9. Wierzbowska A, Robak T, Krawczynska A, Wrzesien-Kus A, Pluta A, Cebula B et al (2005) Circulating endothelial cells in patients with acute myeloid leukemia. Eur J Haematol 75:492–497

    Article  PubMed  Google Scholar 

  10. Mancuso P, Colleoni M, Calleri A, Orlando L, Maisonneuve P, Pruneri G et al (2006) Circulating endothelial-cell kinetics and viability predict survival in breast cancer patients receiving metronomic chemotherapy. Blood 108:452–459

    Article  PubMed  CAS  Google Scholar 

  11. Solovey A, Lin Y, Browne P, Choong S, Wayner E, Hebbel RP (1997) Circulating activated endothelial cells in sickle cell anemia. N Engl J Med 337:1584–1590

    Article  PubMed  CAS  Google Scholar 

  12. Mutin M, Canavy I, Blann A, Bory M, Sampol J, Dignat-George F (1999) Direct evidence of endothelial injury in acute myocardial infarction and unstable angina by demonstration of circulating endothelial cells. Blood 93:2951–2958

    PubMed  CAS  Google Scholar 

  13. Koc M, Richards HB, Bihorac A, Ross EA, Schold JD, Segal MS (2005) Circulating endothelial cells are associated with future vascular events in hemodialysis patients. Kidney Int 67:1078–1083

    Article  PubMed  Google Scholar 

  14. Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S et al (1996) National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 87:4990–4997

    PubMed  CAS  Google Scholar 

  15. Shanafelt TD, Kay NE (2006) The clinical and biologic importance of neovascularization and angiogenic signaling pathways in chronic lymphocytic leukemia. Semin Oncol 33:174–185

    Article  PubMed  CAS  Google Scholar 

  16. Aguayo A, Kantarjian H, Manshouri T, Gidel C, Estey E, Thomas D et al (2000) Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood 96:2240–2245

    PubMed  CAS  Google Scholar 

  17. Gora-Tybor J, Blonski JZ, Robak T (2003) Circulating proangiogenic cytokines and angiogenesis inhibitor endostatin in untreated patients with chronic lymphocytic leukemia. Mediators Inflamm 12:167–171

    Article  PubMed  CAS  Google Scholar 

  18. Molica S, Vitelli G, Levato D, Giannarelli D, Vacca A, Cuneo A et al (2004) Serum angiogenin is not elevated in patients with early B-cell chronic lymphocytic leukemia but is prognostic factor for disease progression. Eur J Haematol 73:36–42

    Article  PubMed  CAS  Google Scholar 

  19. Go RS, Horstman AL (2002) Circulating basic fibroblast growth factor and vascular endothelial growth factor levels in cancer patients: implications for anti-angiogenic therapy. Proc Am Soc Clin Oncol 21:3031 abstr

    Google Scholar 

  20. Shanafelt TD, Geyer S, Bone N, Schwager S, Lee YK, Nowakowski G, et al (2005). Evaluation of the Prognostic Implications of Pro- and Anti-Angiogenic Cytokines in 311 Patients with Untreated Chronic Lymphocytic Leukemia. Blood 106:712 abstr

    Google Scholar 

  21. Molica S, Vitelli G, Levato D, Ricciotti A, Digiesi G (2002) Clinicoprognostic implications of increased serum levels of vascular endothelial growth factor and basic fibroblast growth factor in early B-cell chronic lymphocytic leukaemia. Br J Cancer 86:31–35

    Article  PubMed  CAS  Google Scholar 

  22. Clinical trials. National Cancer Institute. Available at: http://www.nci.nih.gov/search/clinical_trials. Accessed August 6, 2007

  23. Willett CG, Boucher Y, Duda DG, di Tomaso E, Munn LL, Tong RT et al (2005) Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J Clin Oncol 23:8136–8139

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Cancer and Blood Disorders, Gundersen Lutheran Health System, 1900 South Avenue, Mail Stop: EB2-001, 54601, La Crosse, Wisconsin, USA

    Ronald S. Go, Lori A. Meyer, Wayne A. Bottner, Craig E. Cole, John P. Farnen & Kathleen A. Frisby

  2. Microbiology Research Laboratory, Gundersen Lutheran Medical Foundation, La Crosse, Wisconsin, USA

    Dean A. Jobe, Krista E. Asp & Steven M. Callister

  3. Section of Infectious Diseases, Department of Internal Medicine, Gundersen Lutheran Health System, La Crosse, Wisconsin, USA

    Steven M. Callister

  4. Gundersen Lutheran Medical Foundation, La Crosse, Wisconsin, USA

    Michelle A. Mathiason

Authors
  1. Ronald S. Go
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dean A. Jobe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Krista E. Asp
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steven M. Callister
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michelle A. Mathiason
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lori A. Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wayne A. Bottner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Craig E. Cole
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. John P. Farnen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kathleen A. Frisby
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronald S. Go.

Additional information

Supported by the Gundersen Lutheran Center for Cancer and Blood Disorders and the Gundersen Lutheran Medical Foundation.

The Greater Richland Area Cancer Elimination (GRACE), Inc. and the Gundersen Lutheran Medical Foundation funded this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Go, R.S., Jobe, D.A., Asp, K.E. et al. Circulating endothelial cells in patients with chronic lymphocytic leukemia. Ann Hematol 87, 369–373 (2008). https://doi.org/10.1007/s00277-007-0435-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-007-0435-y

Keywords

Search

Navigation