In recent years the plasma proteomes of several different myelodysplastic syndrome (MDS) subgroups have been investigated and compared with those of healthy donors. However, the resulting data do not facilitate a direct and statistical comparison of the changes among the different MDS subgroups that would be useful for the selection and proposal of diagnostic biomarker candidates. The aim of this work was to identify plasma protein biomarker candidates for different MDS subgroups by reanalyzing the proteomic data of four MDS subgroups: refractory cytopenia with multilineage dysplasia (RCMD), refractory anemia or refractory anemia with ringed sideroblasts (RA-RARS), refractory anemia with excess blasts subtype 1 (RAEB-1), and refractory anemia with excess blasts subtype 2 (RAEB-2). Reanalysis of a total of 47 MDS patients revealed biomarker candidates, with alpha-2-HS-glycoprotein and leucine-rich alpha-2-glycoprotein as the most promising candidates.

Clinical Department Institute of Hematology and Blood Transfusion U Nemocnice 1 128 20 Prague 2 Czech Republic

Department of Biochemistry Institute of Hematology and Blood Transfusion U Nemocnice 1 128 20 Prague 2 Czech Republic

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Malcovati L., Hellström-Lindberg E., Bowen D., et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013;122(17):2943–2964. doi: 10.1182/blood-2013-03-492884. PubMed DOI PMC

Vardiman J. W., Harris N. L., Brunning R. D. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100(7):2292–2302. doi: 10.1182/blood-2002-04-1199. PubMed DOI

Vardiman J. W., Thiele J., Arber D. A., et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937–951. doi: 10.1182/blood-2009-03-209262. PubMed DOI

Zemanova Z., Michalova K., Buryova H., et al. Involvement of deleted chromosome 5 in complex chromosomal aberrations in newly diagnosed myelodysplastic syndromes (MDS) is correlated with extremely adverse prognosis. Leukemia Research. 2014;38(5):537–544. doi: 10.1016/j.leukres.2014.01.012. PubMed DOI

Vasikova A., Belickova M., Budinska E., Cermak J. A distinct expression of various gene subsets in CD34+ cells from patients with early and advanced myelodysplastic syndrome. Leukemia Research. 2010;34(12):1566–1572. doi: 10.1016/j.leukres.2010.02.021. PubMed DOI

Cechova H., Lassuthova P., Novakova L., et al. Monitoring of methylation changes in 9p21 region in patients with myelodysplastic syndromes and acute myeloid leukemia. Neoplasma. 2012;59(2):168–174. doi: 10.4149/neo_2012_022. PubMed DOI

Belickova M., Merkerova M. D., Stara E., et al. DNA repair gene variants are associated with an increased risk of myelodysplastic syndromes in a Czech population. Journal of Hematology and Oncology. 2013;6(1, article 9) PubMed PMC

Merkerova M. D., Krejcik Z., Votavova H., Belickova M., Vasikova A., Cermak J. Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome. European Journal of Human Genetics. 2011;19(3):313–319. doi: 10.1038/ejhg.2010.209. PubMed DOI PMC

Votavova H., Grmanova M., Dostalova Merkerova M., et al. Differential expression of MicroRNAs in CD34+ cells of 5q- syndrome. Journal of Hematology and Oncology. 2011;4, article 1 doi: 10.1186/1756-8722-4-1. PubMed DOI PMC

Emmenegger C. R., Brynda E., Riedel T., Sedlakova Z., Houska M., Alles A. B. Interaction of blood plasma with antifouling surfaces. Langmuir. 2009;25(11):6328–6333. doi: 10.1021/la900083s. PubMed DOI

Riedel T., Brynda E., Dyr J. E., Houska M. Controlled preparation of thin fibrin films immobilized at solid surfaces. Journal of Biomedical Materials Research A. 2009;88(2):437–447. doi: 10.1002/jbm.a.31755. PubMed DOI

Rodriguez-Emmenegger C., Brynda E., Riedel T., et al. Polymer brushes showing non-fouling in blood plasma challenge the currently accepted design of protein resistant surfaces. Macromolecular Rapid Communications. 2011;32(13):952–957. doi: 10.1002/marc.201100189. PubMed DOI

Fracchiolla N. S., Artuso S., Cortelezzi A. Biosensors in clinical practice: focus on oncohematology. Sensors. 2013;13(5):6423–6447. doi: 10.3390/s130506423. PubMed DOI PMC

Májek P., Reicheltová Z., Suttnar J., Čermák J., Dyr J. E. Plasma proteome changes associated with refractory cytopenia with multilineage dysplasia. Proteome Science. 2011;9, article 64 doi: 10.1186/1477-5956-9-64. PubMed DOI PMC

Májek P., Reicheltová Z., Suttnar J., Čermák J., Dyr J. E. Plasma protein alterations in the refractory anemia with excess blasts subtype 1 subgroup of myelodysplastic syndrome. Proteome Science. 2012;10(1, article 31) doi: 10.1186/1477-5956-10-31. PubMed DOI PMC

Májek P., Riedelová-Reicheltová Z., Suttnar J., Pečánková K., Čermák J., Dyr J. E. Plasma proteome changes associated with refractory anemia and refractory anemia with ringed sideroblasts in patients with myelodysplastic syndrome. Proteome Science. 2013;11(1, article 14) doi: 10.1186/1477-5956-11-14. PubMed DOI PMC

Majek P., Riedelova-Reicheltova Z., Suttnar J., Pecankova K., Cermak J., Dyr J. E. Proteome changes in the plasma of myelodysplastic syndrome patients with refractory anemia with excess blasts subtype 2. Disease Markers. 2014;2014:8. doi: 10.1155/2014/178709.178709 PubMed DOI PMC

Májek P., Reicheltová Z., Štikarová J., Suttnar J., Sobotková A., Dyr J. E. Proteome changes in platelets activated by arachidonic acid, collagen, and thrombin. Proteome Science. 2010;8, article 56 doi: 10.1186/1477-5956-8-56. PubMed DOI PMC

Májek P., Reicheltová Z., Suttnar J., et al. Plasma proteome changes in cardiovascular disease patients: novel isoforms of apolipoprotein A1. Journal of Translational Medicine. 2011;9, article 84 doi: 10.1186/1479-5876-9-84. PubMed DOI PMC

Holm S. A simple sequentially rejective multiple test procedure. Scandinavian Journal of Statistics. 1979;6(2):65–70.

Petrik V., Saadoun S., Loosemore A., et al. Serum α2-HS glycoprotein predicts survival in patients with glioblastoma. Clinical Chemistry. 2008;54(4):713–722. doi: 10.1373/clinchem.2007.096792. PubMed DOI

Cubedo J., Padró T., Badimon L. Glycoproteome of human apolipoprotein A-I: N- and O-glycosylated forms are increased in patients with acute myocardial infarction. Translational Research. 2014;164(3):209–222. doi: 10.1016/j.trsl.2014.03.008. PubMed DOI

Enroth S., Johansson Å., Enroth S. B., Gyllensten U. Strong effects of genetic and lifestyle factors on biomarker variation and use of personalized cutoffs. Nature Communications. 2014;5, article 4684 doi: 10.1038/ncomms5684. PubMed DOI PMC

Blalock W. L., Bavelloni A., Piazzi M., et al. Multiple forms of PKR present in the nuclei of acute leukemia cells represent an active kinase that is responsive to stress. Leukemia. 2011;25(2):236–245. doi: 10.1038/leu.2010.264. PubMed DOI

Aivado M., Spentzos D., Germing U., et al. Serum proteome profiling detects myelodysplastic syndromes and identifies CXC chemokine ligands 4 and 7 as markers for advanced disease. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(4):1307–1312. doi: 10.1073/pnas.0610330104. PubMed DOI PMC

Fröbel J., Cadeddu R.-P., Hartwig S., et al. Platelet proteome analysis reveals integrin-dependent aggregation defects in patients with myelodysplastic syndromes. Molecular and Cellular Proteomics. 2013;12(5):1272–1280. doi: 10.1074/mcp.M112.023168. PubMed DOI PMC

Beranova-Giorgianni S. Proteome analysis by two-dimensional gel electrophoresis and mass spectrometry: strengths and limitations. TrAC—Trends in Analytical Chemistry. 2003;22(5):273–281. doi: 10.1016/s0165-9936(03)00508-9. DOI

Chen C., Bowen D. T., Giagounidis A. A. N., Schlegelberger B., Haase S., Wright E. G. Identification of disease- and therapy-associated proteome changes in the sera of patients with myelodysplastic syndromes and del(5q) Leukemia. 2010;24(11):1875–1884. doi: 10.1038/leu.2010.182. PubMed DOI

Braoudaki M., Tzortzatou-Stathopoulou F., Anagnostopoulos A. K., et al. Proteomic analysis of childhood de novo acute myeloid leukemia and myelodysplastic syndrome/AML: correlation to molecular and cytogenetic analyses. Amino Acids. 2011;40(3):943–951. doi: 10.1007/s00726-010-0718-9. PubMed DOI

A New Approach for the Diagnosis of Myelodysplastic Syndrome Subtypes Based on Protein Interaction Analysis