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.