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31P MRS analysis of the phospholipid composition of the peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) of patients with acute leukemia (AL)

Abstract

The aim of this study was to evaluate the phospholipid concentration in acute leukemia (AL) blast cells from peripheral blood (PBMC) and bone marrow (BMMC). In vitro 31P Nuclear Magnetic Resonance Spectroscopy (31P MRS) was used. The integral intensities of the resonant peaks and the phospholipid concentrations in PBMC and BMMC were analyzed. Differences in the phospholipid concentrations in cells from myeloblastic or lymphoblastic lines were also evaluated. This investigation was carried out on phospholipid extracts from PBMC and BMMC from 15 healthy volunteers and 77 patients with AL (samples taken at the moment of diagnosis). A significant decrease in sphingomyelin (SM) and phosphtidylserine (PS) was observed in the PBMC of patients with AL relative to the results for the healthy volunteers. For ALL, we found a significant decrease in the concentration of phosphatidylcholine plasmalogen (CPLAS), SM, PI+PE (phosphatidylinositol + phosphatidylethanolamine) and PS in comparison with the results for healthy volunteers and patients with AML. Experiments with BMMC cells revealed a significant decrease in the concentration of CPLAS, SM, PI+PE, and PS in ALL relative to AML. Additionally, a significant decrease in phosphatidylcholine (PC) concentration was observed in ALL compared to AML. If the phospholipid extracts were taken simultaneously from the same patient, there were no significant differences in the integral intensities and phospholipid concentrations between PBMC and BMMC.

Abbreviations

AL:

acute leukemia

ALL:

acute lymphoblastic leukemia

AML:

acute myeloblastic leukemia

BMMC:

bone marrow mononuclear cells

CL:

cardiolipin

CPLAS (PAF):

phosphatidylcholine plasmalogen

FAB:

French-American-British classification

MDPA:

methylenediphosphonic acid

MRS:

magnetic resonance spectroscopy

PBMC:

peripheral blood mononuclear cells

PC:

phosphatidylcholine

PS:

phosphatidylserine

PI+PE:

phosphatidylinositol + phosphatidylethanolamine

SM:

sphingomyelin

References

  1. Kuliszkiewicz-Janus, M. and Baczyński, S. Chemotherapy-associated changes in 31P MRS spectra of sera from patients with multiple myleoma. NMR Biomed. 8 (1995) 127–132.

    PubMed  Article  CAS  Google Scholar 

  2. Kuliszkiewicz-Janus, M. and Baczyński, S. Application of 31P NMR spectroscopy to monitor chemotherapy-associated changes of serum phospholipids in patients with malignant lymphomas. Magn. Reson. Med. 35 (1996) 449–456.

    PubMed  CAS  Google Scholar 

  3. Kuliszkiewicz-Janus, M. and Baczyński, S. Treatment induces changes in 31P MRS (magnetic resonance spectroscopy) spectra of sera from patients with acute leukemia. Biochim. Biophys. Acta 1360 (1997) 71–83.

    PubMed  CAS  Google Scholar 

  4. Kuliszkiewicz-Janus, M., Janus, W. and Baczyński, S. Application of 31P NMR spectroscopy in clinical analysis of changes of serum phospholipids in leukemia, lymphoma and some other non-haematological cancers. Anticancer Res. 16 (1996) 1587–1594.

    PubMed  CAS  Google Scholar 

  5. Kuliszkiewicz-Janus, M., Janus, W., Baczyński, S. and Jurczyk, A. Bone marrow transplantation In the course of hematological malignancies- fellow up to study in blond serum by 31P NMR. Med. Sci. Monit. 10 (2004) 485–492.

    Google Scholar 

  6. Kuliszkiewicz-Janus, M., Tuz, M.A. and Baczyński, S. Application of 31P NMR to the analysis of phospholipids changes in plasma of patients with acute leukemia. Biochim. Biophys. Acta 1737 (2005) 11–15.

    PubMed  CAS  Google Scholar 

  7. Kuliszkiewicz-Janus, M. and Baczyński, S. Phospholipids’ sera and mononuclear cells in acute leukemia, malignant lymphoma and multiple myeloma - evaluation by 31P MRS in vitro. NATO Science Series. II: Mathematics, Physics and Chemistry 76 (2002) 347–354.

    CAS  Google Scholar 

  8. Tuz, M.A., Kuliszkiewicz-Janus, M. and Baczyński, S. Application of 31P NMR magnetic resonance spectroscopy to observation of phospholipids concentration changes in blood serum, plasma, peripheral blood mononuclear cells and bone marrow mononuclear cell from patients with hematological cancers - a methodological review. Polish J. Chem. 80 (2006) 1009–1019.

    CAS  Google Scholar 

  9. Kuliszkiewicz-Janus, M., Tuz, M.A., Kiełbiński, M., Baczyński, S., Jaźwiec, B. and Śladowska, H. Platelet-activating factor changes In phospholipid extracts from plasma, peripheral blood mononuclear cells and bone marrow mononuclear cell of patients with acute leukemia - A 31P NMR in vitro study. Cell. Mol. Biol. Lett. 13 (2008) 58–66.

    PubMed  Article  CAS  Google Scholar 

  10. Kuliszkiewicz-Janus, M., Tuz, M.A., Baczyński, S., Prajs, I. and Jaźwiec, B. 31P NMR analysis of the phospholipid composition of mormal human peripheral blond mononuclear cells (PBMC). Cell. Mol. Biol. Lett. 10 (2005) 373–382.

    PubMed  CAS  Google Scholar 

  11. Merchant, T.E, de Graaf, P.W., Minsky, B.D., Obertop, H. and Glonek, T. Esophageal cancer phospholipid characterization by 31P NMR. NMR Biomed. 6 (1993) 187–193.

    PubMed  Article  CAS  Google Scholar 

  12. Merchant, T.E., Minsky, B.D., Lauwers, G.Y., Diamantis, P.M., Haida, T. and Glonek, T. Esophageal cancer phospholipids correlated with histopathologic findings: A 31P NMR study. NMR Biomed. 12 (1999) 184–188.

    PubMed  Article  CAS  Google Scholar 

  13. van Blitterswijk, W.J., van der Luit, A.H., Veldman, R.J., Verheij, M. and Borst, J. Ceramide: second messenger or modulator of membrane structure and dynamics? Biochem. J. 369 (2003) 199–211.

    PubMed  Article  Google Scholar 

  14. Tepper, A.D., Ruurs, P., Wiedmer, T., Sims, P.J., Borst, J. and van Blitterswijk, W.J. Sphingomyelin hydrolysis to ceramide during the execution phase of apoptosis results from phospholipids scrambling and alters cell-surface morphology. J. Cell Biol. 150 (2000) 155–164.

    PubMed  Article  CAS  Google Scholar 

  15. Bevers, EM., Comfurius, P., Dekkers, D.W. and Zwaal, R.F. Lipid translocation across the plasma membrane of mammalian cells. Biochim. Biophys. Acta 1439 (1999) 317–330.

    PubMed  CAS  Google Scholar 

  16. Verhoven, B., Schlegel, R.A. and Williamson, P. Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lyphocytes. J. Exp. Med. 182 (1995) 1597–1601.

    PubMed  Article  CAS  Google Scholar 

  17. Martin, S.J., Reutelingsperger, C.P., McGahon, A.J., Rader, J.A., van Schie, R.C., LaFace, D.M. and Green, D.R. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J. Exp. Med. 182 (1995) 1545–1556.

    PubMed  Article  CAS  Google Scholar 

  18. Fadok, V.A., Voelker, D.R., Campbell, P.A., Cohen, J.J., Bratton, D.L. and Henson, P.M. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J. Immunol. 148 (1992) 2207–2216.

    PubMed  CAS  Google Scholar 

  19. Kagan, V.E., Fabisiak, J.P., Shvedova, A.A., Tyurina, Y.Y., Tyurin, V.A., Schor, N.F. and Kawai, K. Oxidative signaling pathway for externalization of plasma membrane phosphatidylserine during apoptosis. FEBS Lett. 477 (2000) 1–7.

    PubMed  Article  CAS  Google Scholar 

  20. McConkey, D.J., Zhitovsky, B. and Orrenius, S. Apoptosis — molecular mechanisms and biomedical implications. Mol. Aspects Med. 17 (1996) 1–110.

    PubMed  Article  CAS  Google Scholar 

  21. Eberhardt, C., Gray, P.W. and Tjoelker, L.W. Human lysophosphatidic acid acytylotransferase. CDNA clonning, expression, and localization to chromosome 9q34.3. J. Biol. Chem. 272 (1997) 20299–20305.

    PubMed  Article  CAS  Google Scholar 

  22. Niesporek, S., Denkert, C., Weichert, W., Kobel, M., Noske, A., Sehouli, J., Singer, J.W., Dietel, M. and Hauptmann, S. Expression of lysophosphatidic acid acyltransferase beta (LPAAT-beta) in ovarian carcinoma: correlation with tumour grading and prognosis. Br. J. Cancer 92 (2005) 1729–1736.

    PubMed  Article  CAS  Google Scholar 

  23. Springett, G.M., Bonham, L., Hummer, A., Linkov, I., Misra, D., Ma, C., Pezzoni, G., Di Giovine, S., Singer, J., Kawasaki, H., Spriggs, D., Soslow, R. and Dupont, J. Lysophosphatidic acid acyltransferase-beta is a prognostic marker and therapeutic target in gynecologic malignancies. Cancer Res. 65 (2005) 9415–9425.

    PubMed  Article  CAS  Google Scholar 

  24. Douvas, M.G., Hogan, K.N., Ji, Y., Hollenback, D., Bonham, L., Singer, J.W. and Mitchell, B.S. Effect of lysophosphatidic acid acyltransferase-beta inhibition in acute leukemia. Leuk. Res. 30 (2006) 1027–1036.

    PubMed  Article  CAS  Google Scholar 

  25. Ruiz-Cabello, J. and Cohen, J.S. Phospholipid metabolites as indicators of cancer cell function. NMR Biomed. 5 (1992) 226–233.

    PubMed  CAS  Google Scholar 

  26. Gerhard, A., Häfer, R. and Zintl, F. Fatty acid composition of lymphocyte membrane phospholipids in children with acute leukaemia. Cancer Lett. 173 (2001) 139–144.

    Article  Google Scholar 

  27. Lin, W.C., Manshouri, T., Jilani, I., Neuberg, D., Patel, K., Kantarjian, H., Andreeff, M., Estrov, Z., Beran, M., Keating, M., Estey, E. and Albitar, M. Proliferation and apoptosis in acute and chronic leukemias and myelodysplastic syndrome. Leuk. Res. 26 (2002) 551–559.

    PubMed  Article  Google Scholar 

  28. Shuler, D. and Szende, B. Apoptosis in acute leukaemia. Leuk. Res. 28 (2004) 661–666.

    Article  Google Scholar 

  29. Invernizzi, R., Pecci, A., Bellotti, L. and Ascari, E. Expression of p53, Bcl-2 and Ras oncoproteins and apoptosis levels in acute leukaemias and myelodysplastic syndromes. Leuk. Lymphoma 42 (2001) 481–489.

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Małgorzata Kuliszkiewicz-Janus.

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Kuliszkiewicz-Janus, M., Tuz, M.A., Kiełbiński, M. et al. 31P MRS analysis of the phospholipid composition of the peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) of patients with acute leukemia (AL). Cell Mol Biol Lett 14, 35–45 (2009). https://doi.org/10.2478/s11658-008-0032-7

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  • DOI: https://doi.org/10.2478/s11658-008-0032-7

Key words

  • Acute leukemia
  • 31P MRS
  • Phospholipids