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 G. 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
Externally publishedYes

Fingerprint

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

  • Genetics
  • 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 G.; 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, UG, 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 G. ; 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 G.

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.

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