Serum proteome profiling detects myelodysplastic syndromes and identifies CXC chemokine ligands 4 and 7 as markers for advanced disease
National Academy of Sciences, 2007
academicJournal
Zugriff:
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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Serum proteome profiling detects myelodysplastic syndromes and identifies CXC chemokine ligands 4 and 7 as markers for advanced disease
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Autor/in / Beteiligte Person: | 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. |
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Veröffentlichung: | National Academy of Sciences, 2007 |
Medientyp: | academicJournal |
DOI: | 10.1073/pnas.0610330104 |
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