Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016, 160(1):94-99 | DOI: 10.5507/bp.2015.036

Evaluation of cytokines and soluble adhesion molecules in patients with newly diagnosed acute myeloid leukemia: the role of TNF-alpha and FLT3-ITD

Tomas Kupsaa,b, Jan Vanekc, Martina Vasatovad, Iva Karesovad, Pavel Zakb, Ladislav Jebavya,b, Jan M. Horaceka,b
a Department of Military Internal Medicine and Military Hygiene, University of Defence, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic
b 4th Department of Internal Medicine - Hematology, Faculty of Medicine in Hradec Kralove, Charles University in Prague and University Hospital Hradec Kralove, Czech Republic
c Department of Informatics and Quantitative Methods, , Faculty of Informatics and Management, University of Hradec Kralove, Czech Republic
d Institute of Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove, Czech Republic

Objectives: Acute myeloid leukemia (AML) cells are highly resistant to therapy. The presumed molecular basis of this resistance is the effect of tumor necrosis factor alpha (TNF-α) and other cytokines on endothelial adhesion molecule expression. The aim of this study was to test the hypothesis that cytokines and soluble adhesion molecules correlate in AML.

Methods: Baseline serum levels of 17 cytokines and 5 soluble adhesion molecules were measured in 53 AML patients using biochip array technology. Age, leukocyte count, secondary AML, CRP, FLT3-ITD and remission were variables. Statistical analysis was performed in R version 3.1.2.

Results: VCAM-1 correlated with ICAM-1 (P < 0.0001), E-selectin (P < 0.0001), leukocyte count (P = 0.0005) and TNF-α (P = 0.0035). E-selectin correlated with leukocyte count (P < 0.0001), P-selectin (P = 0.0032) and MCP-1 (P = 0.0119). CRP correlated with IL-6 (P < 0.0001), leukocyte count negatively correlated with IL-7 (P = 0.0318). FLT3-ITD was associated with higher E-selectin (P = 0.0010) and lower IL-7 (P = 0.0252). Secondary AML patients were older. Failure of induction therapy was associated with significantly higher CRP and lower P-selectin. Leukocyte count (P < 0.0001), FLT3-ITD (P = 0.0017) and secondary AML (P = 0.0439) influenced the principal component.

Conclusions: Leukemic cells can modulate the microenvironment. Cytokine, adhesion molecule levels and leukocyte count correlate in AML. Understanding these mechanisms may form the basis of novel therapeutic approaches.

Keywords: cytokines, adhesion molecules, acute myeloid leukemia, TNF-alpha, FLT3-ITD

Received: April 24, 2015; Accepted: July 10, 2015; Prepublished online: September 4, 2015; Published: March 30, 2016  Show citation

ACS AIP APA ASA Harvard Chicago IEEE ISO690 MLA NLM Turabian Vancouver
Kupsa, T., Vanek, J., Vasatova, M., Karesova, I., Zak, P., Jebavy, L., & Horacek, J.M. (2016). Evaluation of cytokines and soluble adhesion molecules in patients with newly diagnosed acute myeloid leukemia: the role of TNF-alpha and FLT3-ITD. Biomedical papers160(1), 94-99. doi: 10.5507/bp.2015.036
Download citation

References

  1. Hatfield K, Øyan AM, Ersvaer E, Kalland KH, Lassalle P, Gjertsen BT, Bruserud Ø. Primary human acute myeloid leukaemia cells increase the proliferation of microvascular endothelial cells through the release of soluble mediators. Br J Hematol 2009;144(1):53-68. Go to original source... Go to PubMed...
  2. Horacek JM, Vasatova M, Kupsa T, Jebavy L, Zak P. Multi-analytical evaluation of serum levels of cytokines and adhesion molecules in patients treated for acute myeloid leukemia using biochip array technology. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013;157(4):277-9. Go to original source... Go to PubMed...
  3. Hatfield KJ, Evensen L, Reikvam H, Lorens JB, Bruserud Ø. Soluble mediators released by acute myeloid leukemia cells increase capillary-like networks. Eur J Haematol 2012;89(6):478-90. Go to original source... Go to PubMed...
  4. Girgis EH, Mahoney JP, Rafaat KH, Soliman MR. Effect of thalidomide and arsenic trioxide on the release of tumor necrosis factor-α and vascular endothelial growth factor from the KG-1a human acute myelogenous leukemia cell line. Oncology letters 2010;1(4):663-7. Go to original source... Go to PubMed...
  5. Volk A, Li J, Xin J, You D, Zhang J, Liu X, Xiao Y, Breslin P, Li Z, Wei W, Schmidt R, Li X, Zhang Z, Kuo PC, Nand S, Zhang J, Chen J, Zhang J. Co-inhibition of NF-κB and JNK is synergistic in TNF-expressing human AML. J Exp Med 2014;211(6):1093-108. Go to original source... Go to PubMed...
  6. Tsimberidou AM, Estey E, Wen S, Pierce S, Kantarjian H, Albitar M, Kurzrock R. The prognostic significance of cytokine levels in newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndromes. Cancer 2008;113(7):1605-13. Go to original source... Go to PubMed...
  7. Scaldaferri F, Sans M, Vetrano S, Correale C, Arena V, Pagano N, Rando G, Romeo F, Potenza AE, Repici A, Malesci A, Danese S. The role of MAPK in governing lymphocyte adhesion to and migration across the microvasculature in inflammatory bowel disease. Eur J Immunol 2009;39(1): 290-300. Go to original source... Go to PubMed...
  8. Zarbock A, Ley K. Neutrophil adhesion and activation under flow. Microcirculation 2009;16(1): 31-42. Go to original source... Go to PubMed...
  9. Stucki A, Rivier AS, Gikic M, Monai N, Schapira M, Spertini O. Endothelial cell activation by myeloblasts: molecular mechanisms of leukostasis and leukemic cell dissemination. Blood 2001;97(7):2121-9. Go to original source... Go to PubMed...
  10. Pezeshkian B, Donnelly C, Tamburo K, Geddes T, Madlambayan GJ. Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell Susceptibility to Chemotherapy through a positive Feedback Loop Mechanism. Plos One 2013; 8(4):e60823. doi:10.1371/journal.pone.0060823. Go to original source... Go to PubMed...
  11. Morandini R, Ghanem G, Portier-Lemarié A, Robaye B, Renaud A, Boeynaems JM. Action of cAMP on expression and release of adhesion molecules in human endothelial cells. Am J Physiol 1996;(7)270:807-16. Go to original source... Go to PubMed...
  12. Becker PS, Kopecky KJ, Wilks AN, Chien S, Harlan JM, Willman CL, Petersdorf SH, Stirewalt DL, Papayannopoulou T, Appelbaum FR. Very late antigen-4 function of myeloblasts correlates with improved overall survival for patients with acute myeloid leukemia. Blood 2009;113(4): 866-74. Go to original source... Go to PubMed...
  13. Hothorn T, Hornik K, van de Wiel MA, Zeileis A. Implementing a Class of Permutation Tests: The coin Package. Journal of Statistical Software 2008;28(8):1-23. Go to original source... Go to PubMed...
  14. Holm S. A simple sequentially rejective multiple test procedure. Scandinavian Journal of Statistics 1979;6(2):65-70.
  15. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420(6917):860-7. Go to original source... Go to PubMed...
  16. Kupsa T, Horacek JM, Jebavy L. The role of cytokines in acute myeloid leukemia: a systematic review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2012;156(4):291-301. Go to original source... Go to PubMed...
  17. Hsu H, Lee Y, Tsai W, Jiang ML, Ho CH, Ho CK, Wang SY. Circulating levels of thrombopoietic and inflammatory cytokines in patients with acute myeloblastic leukemia and myelodysplastic syndrome. Oncology 2002;63(1):64-9. Go to original source... Go to PubMed...
  18. Egberts JH, Cloosters V, Noack A, Schniewind B, Thon L, Klose S, Kettler B, von Forstner C, Kneitz C, Tepel J, Adam D, Wajant H, Kalthoff H, Trauzold A. Anti-tumor necrosis factor therapy inhibits pancreatic tumor growth and metastasis. Cancer Res 2008;68(5):1443-50. Go to original source... Go to PubMed...
  19. Popivanova BK, Kitamura K, Wu Y, Kondo T, Kagaya T, Kaneko S, Oshima M, Fujii C, Mukaida N. Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. J Clin Invest 2008;118(2):560-70. Go to original source... Go to PubMed...
  20. Stroncek D, Slezak S, Khuu H, Basil C, Tisdale J, Leitman SF, Marincola FM, Panelli MC. Proteomic signature of myeloproliferation and neutrophilia: analysis of serum and plasma from healthy subjects given granulocyte colony-stimulating factor. Exp Hematol 2005;33(10):1109-17. Go to original source... Go to PubMed...
  21. Kornblau SM, McCue D, Singh N, Chen W, Estrov Z, Coombes KR. Recurrent expression signatures of cytokines and chemokines are present and are independently prognostic in acute myelogenous leukemia and myelodysplasia. Blood 2010;116(20):4251-61. Go to original source... Go to PubMed...
  22. Estrov Z, Black RA, Sleath PR, Harris D, Van Q, LaPushin R, Estey EH, Talpaz M. Effect of interleukin-1 beta converting enzyme inhibitor on acute myelogenous leukemia progenitor proliferation. Blood 1995;86(12):4594-602. Go to original source...
  23. Dokter WH, Tuyt L, Sierdsema SJ, Esselink MT, Vellenga E. The spontaneous expression of interleukin-1 beta and interleukin-6 is associated with spontaneous expression of AP-1 and NF-kappa B transcription factor in acute myeloblastic leukemia cells. Leukemia 1995;9(3):425-32. Go to PubMed...
  24. Gouilleux-Gruart V, Gouilleux F, Desaint C, Claisse JF, Capiod JC, Delobel J, Weber-Nordt R, Dusanter-Fourt I, Dreyfus F, Groner B, Prin L. STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients. Blood 1996;87(5):1692-7. Go to original source... Go to PubMed...
  25. Sanchez-Correa B, Bergua JM, Campos C, Gayoso I, Arcos MJ, Bañas H, Morgado S, Casado JG, Solana R, Tarazona R. Cytokine profiles in acute myeloid leukemia patients at diagnosis: survival is inversely correlated with IL-6 and directly correlated with IL-10 levels. Cytokine 2013;61(3):885-91. Go to original source... Go to PubMed...