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