Identification of disease- and therapy-associated proteome changes in the sera of patients with myelodysplastic syndromes and del(5q)

Abstract

Using ProteinChip array technology, which is based on the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed proteomic analyses on sera from myelodysplastic syndromes (MDSs) patients with an interstitial deletion of the long arm of chromosome 5 (del(5q)) and those from control individuals. One analysis with 80 samples from 29 patients and 51 control subjects resulted in the detection of 61 peak differences. Another analysis with 36 paired-samples from 18 patients collected before and after the treatment with lenalidomide (Revlimid) identified 19 differential peak features. We also observed differential profiles between the pre-treatment samples from the responders and those from the non-responders reflected by eight peak differences. On the basis of these data we developed two classification models that could distinguish between the diseased and the control subjects or between the responders and the non-responders. Efforts were made to purify and identify a range of differential peak proteins. We conclude that inter-a trypsin inhibitor, heavy chain H4 (fragments), serum transferrin, transthyretin (variants), haemoglobin and a protein peak at m/z 2791 could be potential disease-associated markers for del(5q) MDS. Platelet factor 4 (PF-4) and a peak at m/z 8559 may serve as therapy-associated markers and be potentially useful for monitoring and predicting the response to therapy.

Plasma protein alterations in the refractory anemia with excess blasts subtype 1 subgroup of myelodysplastic syndrome

“…The results obtained by 2-DE concerning ITIH4 fragments may be explained by a progressive fragmentation of ITIH4 fragments in the patient group producing smaller fragments (which could not be detected by 2-DE as used in our study); as well as also the possibility of posttranslational modifications. Nevertheless, in light of the observations from RAEB-1, RCMD, and previous literature [17] it seems that ITIH4 alterations could be a marker specific for myelodysplastic syndrome.…”

“…ITIH4 is a protein involved in acute phase reaction and is considered to be a possible marker of cancer [16]. Its fragments have been found to be potentially associated with MDS [17]; with differences in the fragmentation of ITIH4 having been shown in literature [16,18] and related to several malignant diseases [18-21]. Moreover, changes in the composition or modifications in ITIH4 fragments were observed in our previous proteomic study describing plasma proteome changes in another MDS subgroup – refractory cytopenia with multilineage dysplasia (RCMD) [22].…”

Plasma proteome changes associated with refractory cytopenia with multilineage dysplasia

“…ITIH4 fragments have been found to be potentially associated with MDS [9]; and several authors have shown differences in the fragmentation of ITIH4 [21,22]. Furthermore, an alternation in ITIH4 fragments has been described in several malignant diseases [22-25].…”

“…Complex protein-protein networks reflect the changes at the transcription level, as well as changes induced by protein modifications depending on (patho) physiological conditions in organisms. Posttranslational modifications of proteins including fragmentation or cross-linking are examples of changes detected exclusively by proteomic techniques [8], which may play a crucial role in the development and progression of the disease [9,10]. …”

Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia

“…Previous studies have implicated serum levels of CXCL4 and CXCL7 as potential prognostic markers in MDS (61,62). To determine whether serum levels of CXCL4 and CXCL7 could potentially serve as biomarkers for DAC response, we quantified the serum concentrations of these chemokines by ELISAs in 35 of 40 CMML patients (Supplemental Figure 6).…”