Serum proteome profiling detects myelodysplastic syndromes and identifies CXC chemokine ligands 4 and 7 as markers for advanced disease

Manuel Aivado, Dimitrios Spentzos, Ulrich Germing, Gil Alterovitz, Xiao Ying Meng, Franck Grall, Aristoteles A.N. Giagounidis, Giannoula Klement, Ulrich Steidl, Hasan H Otu, Akos Czibere, Wolf C. Prall, Christof Iking-Konert, Michelle Shayne, Marco F. Ramoni, Norbert Gattermann, Rainer Haas, Constantine S. Mitsiades, Eric T. Fung, Towia A. Libermann

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Myelodysplastic syndromes (MDS) are among the most frequent hematologic malignancies. Patients have a short survival and often progress to acute myeloid leukemia. The diagnosis of MDS can be difficult; there is a paucity of molecular markers, and the pathophysiology is largely unknown. Therefore, we conducted a multicenter study investigating whether serum proteome profiling may serve as a noninvasive platform to discover novel molecular markers for MDS. We generated serum proteome profiles from 218 individuals by MS and identified a profile that distinguishes MDS from non-MDS cytopenias in a learning sample set. This profile was validated by testing its ability to predict MDS in a first independent validation set and a second, prospectively collected, independent validation set run 5 months apart. Accuracy was 80.5% in the first and 79.0% in the second validation set. Peptide mass fingerprinting and quadrupole TOF MS identified two differential proteins: CXC chemokine ligands 4 (CXCL4) and 7 (CXCL7), both of which had significantly decreased serum levels in MDS, as confirmed with independent antibody assays. Western blot analyses of platelet lysates for these two platelet-derived molecules revealed a lack of CXCL4 and CXCL7 in MDS. Subtype analyses revealed that these two proteins have decreased serum levels in advanced MDS, suggesting the possibility of a concerted disturbance of transcription or translation of these chemokines in advanced MDS.

Original languageEnglish (US)
Pages (from-to)1307-1312
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number4
DOIs
StatePublished - Jan 23 2007

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CXC Chemokines
Myelodysplastic Syndromes
Proteome
Ligands
Serum
Blood Platelets
Aptitude
Peptide Mapping
Hematologic Neoplasms
Chemokines
Acute Myeloid Leukemia
Multicenter Studies
Proteins
Western Blotting
Learning
Survival

Keywords

  • Biomarker
  • Chemokine
  • Hematologic malignancy
  • Proteomics

ASJC Scopus subject areas

  • General

Cite this

Serum proteome profiling detects myelodysplastic syndromes and identifies CXC chemokine ligands 4 and 7 as markers for advanced disease. / Aivado, Manuel; Spentzos, Dimitrios; Germing, Ulrich; Alterovitz, Gil; Meng, Xiao Ying; Grall, Franck; Giagounidis, Aristoteles A.N.; Klement, Giannoula; Steidl, Ulrich; Otu, Hasan H; Czibere, Akos; Prall, Wolf C.; Iking-Konert, Christof; Shayne, Michelle; Ramoni, Marco F.; Gattermann, Norbert; Haas, Rainer; Mitsiades, Constantine S.; Fung, Eric T.; Libermann, Towia A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 4, 23.01.2007, p. 1307-1312.

Research output: Contribution to journalArticle

Aivado, M, Spentzos, D, Germing, U, Alterovitz, G, Meng, XY, Grall, F, Giagounidis, AAN, Klement, G, Steidl, U, Otu, HH, Czibere, A, Prall, WC, Iking-Konert, C, Shayne, M, Ramoni, MF, Gattermann, N, Haas, R, Mitsiades, CS, Fung, ET & Libermann, TA 2007, '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, vol. 104, no. 4, pp. 1307-1312. https://doi.org/10.1073/pnas.0610330104
Aivado, Manuel ; Spentzos, Dimitrios ; Germing, Ulrich ; Alterovitz, Gil ; Meng, Xiao Ying ; Grall, Franck ; Giagounidis, Aristoteles A.N. ; Klement, Giannoula ; Steidl, Ulrich ; Otu, Hasan H ; Czibere, Akos ; Prall, Wolf C. ; Iking-Konert, Christof ; Shayne, Michelle ; Ramoni, Marco F. ; Gattermann, Norbert ; Haas, Rainer ; Mitsiades, Constantine S. ; Fung, Eric T. ; Libermann, Towia A. / Serum proteome profiling detects myelodysplastic syndromes and identifies CXC chemokine ligands 4 and 7 as markers for advanced disease. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 4. pp. 1307-1312.
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AU - Aivado, Manuel

AU - Spentzos, Dimitrios

AU - Germing, Ulrich

AU - Alterovitz, Gil

AU - Meng, Xiao Ying

AU - Grall, Franck

AU - Giagounidis, Aristoteles A.N.

AU - Klement, Giannoula

AU - Steidl, Ulrich

AU - Otu, Hasan H

AU - Czibere, Akos

AU - Prall, Wolf C.

AU - Iking-Konert, Christof

AU - Shayne, Michelle

AU - Ramoni, Marco F.

AU - Gattermann, Norbert

AU - Haas, Rainer

AU - Mitsiades, Constantine S.

AU - Fung, Eric T.

AU - Libermann, Towia A.

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N2 - Myelodysplastic syndromes (MDS) are among the most frequent hematologic malignancies. Patients have a short survival and often progress to acute myeloid leukemia. The diagnosis of MDS can be difficult; there is a paucity of molecular markers, and the pathophysiology is largely unknown. Therefore, we conducted a multicenter study investigating whether serum proteome profiling may serve as a noninvasive platform to discover novel molecular markers for MDS. We generated serum proteome profiles from 218 individuals by MS and identified a profile that distinguishes MDS from non-MDS cytopenias in a learning sample set. This profile was validated by testing its ability to predict MDS in a first independent validation set and a second, prospectively collected, independent validation set run 5 months apart. Accuracy was 80.5% in the first and 79.0% in the second validation set. Peptide mass fingerprinting and quadrupole TOF MS identified two differential proteins: CXC chemokine ligands 4 (CXCL4) and 7 (CXCL7), both of which had significantly decreased serum levels in MDS, as confirmed with independent antibody assays. Western blot analyses of platelet lysates for these two platelet-derived molecules revealed a lack of CXCL4 and CXCL7 in MDS. Subtype analyses revealed that these two proteins have decreased serum levels in advanced MDS, suggesting the possibility of a concerted disturbance of transcription or translation of these chemokines in advanced MDS.

AB - Myelodysplastic syndromes (MDS) are among the most frequent hematologic malignancies. Patients have a short survival and often progress to acute myeloid leukemia. The diagnosis of MDS can be difficult; there is a paucity of molecular markers, and the pathophysiology is largely unknown. Therefore, we conducted a multicenter study investigating whether serum proteome profiling may serve as a noninvasive platform to discover novel molecular markers for MDS. We generated serum proteome profiles from 218 individuals by MS and identified a profile that distinguishes MDS from non-MDS cytopenias in a learning sample set. This profile was validated by testing its ability to predict MDS in a first independent validation set and a second, prospectively collected, independent validation set run 5 months apart. Accuracy was 80.5% in the first and 79.0% in the second validation set. Peptide mass fingerprinting and quadrupole TOF MS identified two differential proteins: CXC chemokine ligands 4 (CXCL4) and 7 (CXCL7), both of which had significantly decreased serum levels in MDS, as confirmed with independent antibody assays. Western blot analyses of platelet lysates for these two platelet-derived molecules revealed a lack of CXCL4 and CXCL7 in MDS. Subtype analyses revealed that these two proteins have decreased serum levels in advanced MDS, suggesting the possibility of a concerted disturbance of transcription or translation of these chemokines in advanced MDS.

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