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

Authors

• Manuel Aivado, Harvard Medical School
• Dimitrios Spentzos, Harvard Medical School
• Ulrich Germing, Heinrich Heine University
• Gil Alterovitz, Harvard Partners Center for Genetics and Genomics
• Xiao-Ying Meng, Ciphergen Biosystems, Inc.
• Franck Grall, Harvard Medical School
• Aristoteles A. N. Giagounidis, Heinrich Heine University
• Giannoula Klement, Boston Childrens Hospital
• Ulrich Steidl, Harvard Medical School
• Hasan H. Otu, University of Nebraska-LincolnFollow
• Akos Czibere, Harvard Medical School
• Wolf C. Prall, Harvard Medical School
• Christof Iking-Konert, Heinrich Heine University
• Michelle Shayne, Harvard Medical School
• Marco F. Ramoni, Harvard Partners Center for Genetics and Genomics
• Norbert Gattermann, Heinrich Heine University
• Rainer Haas, Heinrich Heine University
• Constantine S. Mitsiades, Harvard Cancer Center
• Eric T. Fung, Ciphergen Biosystems, Inc.
• Towia A. Libermann, Harvard Medical SchoolFollow

Document Type

Article

Date of this Version

2007

Citation

PNAS, January 23, 2007; vol. 104, no. 4, 1307–1312

Comments

© 2007 by The National Academy of Sciences of the USA

www.pnas.org/cgi/doi/10.1073/pnas.0610330104

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.