Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter March 25, 2015

Changes in cell death of peripheral blood lymphocytes isolated from children with acute lymphoblastic leukemia upon stimulation with 7 Hz, 30 mT pulsed electromagnetic field

  • Jolanta Kaszuba-Zwoińska , Magdalena Ćwiklińska , Walentyna Balwierz , Paulina Chorobik , Bernadeta Nowak , Karolina Wójcik-Piotrowicz , Agata Ziomber , Kinga Malina-Novak , Wiesław Zaraska and Piotr J. Thor EMAIL logo

Abstract

Pulsed electromagnetic field (PEMF) influenced the viability of proliferating in vitro peripheral blood mononuclear cells (PBMCs) isolated from Crohn’s disease patients as well as acute myeloblastic leukemia (AML) patients by induction of cell death, but did not cause any vital changes in cells from healthy donors. Experiments with lymphoid U937 and monocytic MonoMac6 cell lines have shown a protective effect of PEMF on the death process in cells treated with death inducers.The aim of the current study was to investigate the influence of PEMF on native proliferating leukocytes originating from newly diagnosed acute lymphoblastic leukemia (ALL) patients.

The effects of exposure to PEMF were studied in PBMCs from 20 children with ALL. PBMCs were stimulated with three doses of PEMF (7 Hz, 30 mT) for 4 h each with 24 h intervals. After the last stimulation, the cells were double stained with annexin V and propidium iodide dye to estimate viability by flow cytometric analysis.The results indicated an increase of annexin V positive as well as double stained annexin V and propidium iodide positive cells after exposure to threefold PEMF stimulation.

A low-frequency pulsed electromagnetic field induces cell death in native proliferating cells isolated from ALL patients. The increased vulnerability of proliferating PBMCs to PEMF-induced interactions may be potentially applied in the therapy of ALL.The analysis of expression of apoptosis-related genes revealed changes in mRNA of some genes engaged in the intrinsic apoptotic pathway belonging to the Bcl-2 family and the pathway with apoptosis-inducing factor (AIF) abundance upon PEMF stimulation of PBMCs.

References

1. Lim, J.Y., Bhatia, S., Robison, L.L. and Yang, J.J. Genomics of racial and ethnic disparities in childhood acute lymphoblastic leukemia. Cancer 120 (2014) 955-962. DOI: 10.1002/cncr.28531.10.1002/cncr.28531Search in Google Scholar PubMed PubMed Central

2. Hasle, H., Clemmensen, I.H. and Mikkelsen, M. Risks of leukaemia and solid tumours in individuals with Down’s syndrome. Lancet 355 (2000) 165-169.Search in Google Scholar

3. Mullighan, C.G., Collins-Underwood, J.R., Phillips, L.A., Loudin, M.G., Liu, W., Zhang, J., Ma, J., Coustan-Smith, E., Harvey, R.C., Willman, C.L., Mikhail, F.M., Meyer, J., Carroll, A.J., Williams, R.T., Cheng, J., Heerema, N.A., Basso, G., Pession, A., Pui, C.H., Raimondi, S.C., Hunger, S.P., Downing, J.R., Carroll, W.L. and Rabin, K.R. Rearrangement of CRLF2 in B-progenitorand Down syndrome-associated acute lymphoblastic leukemia. Nat Genet. 41 (2009) 1243-1246.Search in Google Scholar

4. Pui, C.H., Mullighan, C.G., Evans, W.E. and Relling, M.V. Pediatric acute lymphoblastic leukemia: Where are we going and how do we get there? Blood 120 (2012) 1165-1174.Search in Google Scholar

5. McNeer, J.L. and Raetz, E.A. Acute lymphoblastic leukemia in young adults: Which treatment? Curr. Opin. Oncol. 24 (2012) 487-494.10.1097/CCO.0b013e32835538f8Search in Google Scholar PubMed

6. Bauer, J., Jurgens, H. and Fruhwald, M.C. Important aspects of nutrition in children with cancer. Adv. Nutr. 2 (2011) 67-77.Search in Google Scholar

7. Owens, J.L., Hanson, S.J., McArthur, J.A. and Mikhailov, T.A. The need for evidence based nutritional guidelines for pediatric acute lymphoblastic leukemia patients: acute and long-term following treatment. Nutrients 5 (2013) 4333-4346.Search in Google Scholar

8. Astolfi, A., Vendemini, F., Urbini, M., Melchionda, F., Masetti, R., Franzoni, M., Libri, V., Serravalle, S., Togni, M., Paone, G., Montemurro,L., Bressanin, D., Chiarini,F., Martelli, A.M., Tonelli, R. and Pession, A. MYCN is a novel oncogenic target in pediatric T-cell Acute Lymphoblastic Leukemia. Oncotarget 5 (2014) 120-130.Search in Google Scholar

9. Goldberg, J.M., Silverman, L.B., Levy, D.E., Dalton, V.K., Gelber, R.D., Lehmann, L., Cohen, H.J., Sallan, S.E. and Asselin, B.L. Childhood T-cell acute lymphoblastic leukemia: the Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience. J. Clin. Oncol. 21 (2003) 3616-3622.Search in Google Scholar

10. Pui, C.H. and Evans, W.E. Treatment of acute lymphoblastic leukemia. N. Engl. J. Med. 354 (2006) 166-168.Search in Google Scholar

11. Ferrando, A.A., Neuberg, D.S., Staunton, J., Loh, M.L., Huard, C., Raimondi, S.C., Behm, F.G., Pui C.H., Downing, J.R., Gilliland, D.G., Lander, E.S., Golub, T.R. and Look, A.T. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 1 (2002) 75-87.Search in Google Scholar

12. Chiarini, F., Grimaldi, C., Ricci, F., Tazzari, P.L., Evangelisti, C., Ognibene, A., Battistelli, M., Falcieri, E., Melchionda, F., Pession, A., Pagliaro, P., McCubrey, J.A. and Martelli, A.M. Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against T-cell acute lymphoblastic leukemia. Cancer Res. 70 (2010) 8097-8107.Search in Google Scholar

13. Pession, A., Masetti, R., Kleinschmidt, K. and Martoni, A. Use of clofarabine for acute childhood leukemia. Biologics 4 (2010) 111-118.Search in Google Scholar

14. McCubrey, J.A., Steelman, L.S., Chappell, W.H., Sun, L., Davis, N.M., Abrams, S.L., Franklin, R.A., Cocco, L., Evangelisti, C., Chiarini, F., Martelli, A.M., Libra, M., Candido, S., Ligresti, G., Malaponte, G., Mazzarino, M.C., Fagone, P., Donia, M., Nicoletti, F., Polesel, J., Talamini, R., Bäsecke, J., Mijatovic, S., Maksimovic-Ivanic, D., Michele, M., Tafuri, A., Dulińska-Litewka, J., Laidler, P., D'Assoro, A.B., Drobot, L., Umezawa, D., Montalto, G., Cervello, M. and Demidenko, Z.N. Advances in targeting signal transduction pathways. Oncotarget 3 (2012) 1505-1521.Search in Google Scholar

15. Martelli, A.M., Chiarini, F., Evangelisti, C., Cappellini, A., Buontempo, F., Bressanin, D., Fini, M. and McCubrey, J.A. Two hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment. Oncotarget 3 (2012) 371-394.Search in Google Scholar

16. Bressanin, D., Evangelisti, C., Ricci, F., Tabellini, G., Chiarini, F., Tazzari, P.L., Melchionda, F., Buontempo, F., Pagliaro, P., Pession, A., McCubrey, J.A. and Martelli, A.M. Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels. Oncotarget 3 (2012) 811-823.Search in Google Scholar

17. Kelly, P.N. and Strasser, A. The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy. Cell Death Differ. 18 (2011) 1414-1424.Search in Google Scholar

18. D'Angelo, V., Crisci, S., Casale, F., Addeo, R., Giuliano, M., Pota, E., Finsinger, P., Baldi, A., Rondelli, R., Abbruzzese, A., Caraglia, M. and Indolfi, P. HighErk-1 activation and Gadd45a expression asprognostic markers in high risk pediatric haemolymphoproliferative diseases. J. Exp.Clin.Cancer Res. 19 (2009) 28-39.Search in Google Scholar

19. Oltersdorf, T., Elmore, S.W., Shoemaker, A.R., Armstrong, R.C., Augeri, D.J., Belli, B.A., Bruncko, M., Deckwerth, T.L., Dinges, J., Hajduk, P.J., Joseph, M.K., Kitada, S., Korsmeyer, S.J., Kunzer, A.R., Letai, A., Li, C., Mitten, M.J., Nettesheim, D.G., Ng, S., Nimmer, P.M., O'Connor, J.M., Oleksijew, A., Petros, A.M., Reed, J.C., Shen, W., Tahir, S.K., Thompson, C.B., Tomaselli, K.J., Wang, B., Wendt, M.D., Zhang, H., Fesik, S.W. and Rosenberg, S.H. An inhibitor of Bcl-2 family proteins induces regression of solid tumors. Nature 435 (2005) 677-681.Search in Google Scholar

20. Lock, R., Carol, H., Houghton, P.J., Morton, C.L., Kolb, E.A., Gorlick, R., Reynolds, C.P., Maris, J.M., Keir, S.T., Wu, J. and Smith, M.A. Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr. Blood Cancer 50 (2008) 1181-1189.Search in Google Scholar

21. Kaszuba-Zwoińska,. J., Zdziłowska, E., Chorobik, P., Słodowska-Hajduk, Z., Juszczak, K., Zaraska, W. and Thor, P. Pulsing Electromagnetic Field and Death of Proliferating Peripheral Blood Mononuclear Cells from Patients with Acute Myelogenic Leukemia. Adv. Clin. Exp. Med. 20 (2011) 721-727.Search in Google Scholar

22. Gluck, B., Guntzschel, V. and Berg, H. Inhibition of proliferation of human lymphoma cells U937 by a 50 Hz electromagnetic field. Cell. Mol. Biol. 47 (2001) 115-117.Search in Google Scholar

23. Kaszuba-Zwoińska, J., Ciećko-Michalska, I., Madroszkiewicz, D., Mach, T., Słodowska-Hajduk, Z., Rokita, E., Zaraska, W. and Thor, P. Magnetic field anti-inflammatory effects in Crohn's disease depends upon viability and cytokine profile of the immune competent cells. J. Physiol. Pharmacol. 59 (2008) 177-187.Search in Google Scholar

24. Kaszuba-Zwoinska, J., Wojcik, K., Bereta, M., Ziomber, A., Pierzchalski, P., Rokita, E., Marcinkiewicz, J., Zaraska, W., and Thor, P. Pulsating electromagnetic field stimulation prevents cell death of puromycin treated U937 cell line. J. Physiol. Pharmacol. 61 (2010) 201-205.Search in Google Scholar

25. Kaszuba-Zwoinska, J., Chorobik, P., Juszczak, K., Zaraska, W. and Thor, P.J. Pulsed electromagnetic field affects intrinsic and endoplasmatic reticulum apoptosis induction pathways in MonoMac6 cell line culture. J. Physiol. Pharmacol. 63 (2012) 537-545.Search in Google Scholar

26. Lai, H. and Singh, N.P. Acute exposure to a 60 Hz magnetic field increases DNA strand breaks in rat brain cells. Bioelectromagnetics 18 (1997) 156-165.Search in Google Scholar

27. Aref, S., Salama, O., Al-Tonbary, Y. and Mansour, A. Assessment of Bcl-2 expression as modulator of Fas mediated apoptosis in acute leukemia. Hematology 9 (2004) 113-121.Search in Google Scholar

28. Coustan-Smith, E., Kitanaka, A., Pui, C.H., McNinch, L., Evans, W.E., Raimondi, S.C., Behm, F.G., Aricò, M. and Campana, D. Clinical relevance of BCL-2 overexpression in childhood acute lymphoblastic leukemia. Blood 87 (1996) 1140-1146.Search in Google Scholar

29. Hogarth, A.L. and Hall, G.A. Increased BAX expression is associated with an increased risk of relapse in childhood acute lymphoblastic leukemia. Blood 93 (1996) 2671-2678.Search in Google Scholar

30. Prokop, A., Wieder, T., Sturm, I., Essmann, F., Seeger, K., Wuchter, C., Ludwig, W.D., Henze, G., Dörken, B. and Daniel, P.T. Relapsein childhood acute lymphoblastic leukemia is associated with a decrease of the Bax/Bcl-2 ratio and loss of spontaneous caspase-3 processing in vivo. Leukemia 14 (2000) 1606-1613.Search in Google Scholar

31. Kaparou, M., Choumerianou, D., Perdikogianni, C., Martimianaki, G., Kalmanti, M. and Stiakaki, E. Enhanced levels of the apoptotic BAX/BCL-2 ratio in children with acute lymphoblastic leukemia and high-risk features. Genet. Mol. Biol. 36 (2013) 7-11. Search in Google Scholar

Received: 2014-6-4
Accepted: 2015-1-26
Published Online: 2015-3-25
Published in Print: 2015-3-1

© 2015 University of Wrocław, Poland

Downloaded on 23.4.2024 from https://www.degruyter.com/document/doi/10.1515/cmble-2015-0006/html
Scroll to top button