title: Serum proteome profiling detects myelodysplastic syndromes and identifies CXC chemokine ligands 4 and 7 as markers for advanced disease.
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.
authors.affiliation: Proteomics Core and Department of Medical Oncology, Dana-Farber/Harvard Cancer Center, Boston, MA 02115, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Aivado
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Spentzos
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.forename: Gil
authors.initials: G
authors.lastname: Alterovitz
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Meng
authors.forename: Franck
authors.initials: F
authors.lastname: Grall
authors.forename: Aristoteles A N
authors.initials: AA
authors.lastname: Giagounidis
authors.forename: Giannoula
authors.initials: G
authors.lastname: Klement
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steidl
authors.forename: Hasan H
authors.initials: HH
authors.lastname: Otu
authors.forename: Akos
authors.initials: A
authors.lastname: Czibere
authors.forename: Wolf C
authors.initials: WC
authors.lastname: Prall
authors.forename: Christof
authors.initials: C
authors.lastname: Iking-Konert
authors.forename: Michelle
authors.initials: M
authors.lastname: Shayne
authors.forename: Marco F
authors.initials: MF
authors.lastname: Ramoni
authors.forename: Norbert
authors.initials: N
authors.lastname: Gattermann
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Mitsiades
authors.forename: Eric T
authors.initials: ET
authors.lastname: Fung
authors.forename: Towia A
authors.initials: TA
authors.lastname: Libermann
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D001798:Blood Proteins / Q000737:chemistry*; D019743:Chemokines, CXC / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D009190:Myelodysplastic Syndromes / Q000097:blood*; D020543:Proteome
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D019743:Chemokines, CXC; D020543:Proteome