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Serum peptidome based biomarkers searching for monitoring minimal residual disease in adult acute lymphocytic leukemia.

Bai J, He A, Huang C, Yang J, Zhang W, Wang J, Yang Y, Zhang P, Zhang Y, Zhou F - Proteome Sci (2014)

Bottom Line: Relative intensities of the five peptides were compared among ALL different groups for the potential importance of MRD evaluation in ALL.Peptides with decreased relative intensities in ND and RR ALL patients were found to be increased in their relative intensities when ALL patients achieved CR.The findings were validated by ELISA and western blot.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, 710004 Shaanxi Province China.

ABSTRACT

Background: The persistence of minimal residual disease (MRD) during therapy is the strongest adverse prognostic factor in acute lymphocytic leukemia (ALL). This study was to identify serum candidate peptides for monitoring MRD in adult ALL.

Results: A total of 33 peptides in the molecular weight range of 1000-10000 Da were detected using ClinProt system and statistically different between adult patients with ALL and healthy controls. Quick classifier (QC) algorithm was used to obtain a diagnostic model consisting of five peptides that could discriminate patients with ALL from controls with a high sensitivity (100%) and specificity (96.67%). The peptides in the QC model were identified as fibrinogen alpha chain (FGA), glutathione S-transferase P1 (GSTP1), isoform 1 of fibrinogen alpha chain precursor, platelet factor 4 (PF4) by high pressure/performance liquid chromatography mass spectrometry/mass spectrometry. Relative intensities of the five peptides were compared among ALL different groups for the potential importance of MRD evaluation in ALL. The peptides with increased relative intensities in newly diagnosed (ND) ALL patients were found to be decreased in their relative intensities after complete remission (CR) of adult ALL. When ALL patients were refractory & relapsed (RR), relative intensities of the peptides were elevated again. Peptides with decreased relative intensities in ND and RR ALL patients were found to be increased in their relative intensities when ALL patients achieved CR. The findings were validated by ELISA and western blot. Further linear regression analyses were performed to eliminate the influence of platelet and white blood cell counts on serum protein contents and indicated that there were no correlations between the contents of all four proteins (PF4, connective tissue active peptide III, FGA and GSTP1) and white blood cell or platelet counts in ALL different groups and healthy control.

Conclusions: We speculate the five peptides, FGA, isoform 1 of fibrinogen alpha chain precursor, GSTP1, PF4 and connective tissue active peptide III would be potential biomarkers for forecasting relapse, monitoring MRD and evaluating therapeutic response in adult ALL.

No MeSH data available.


Related in: MedlinePlus

Serum peptide fingerprints and cluster analysis of newly diagnosed ALL and healthy control. A. Comparison of serum peptide fingerprints between ALL patients and healthy controls showed that peak number and intensity of the two groups were completely different. B. Stack view of comparison between ALL patients and healthy controls. (Red: ALL newly diagnosed group Green: Healthy control group).
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Fig1: Serum peptide fingerprints and cluster analysis of newly diagnosed ALL and healthy control. A. Comparison of serum peptide fingerprints between ALL patients and healthy controls showed that peak number and intensity of the two groups were completely different. B. Stack view of comparison between ALL patients and healthy controls. (Red: ALL newly diagnosed group Green: Healthy control group).

Mentions: Despite varying peptide masses and spectrum intensities, the peak coefficient of variations (CVs) were all <14% in the within-run assays and <22% in the between-run assays. The CV value of the relative intensity of each peak in MALDI-TOF-MS was less than 30%, indicating that ClinProt system had good repeatability [25]. To screen serum peptides of interest for adult ALL, comparative analyses of serum peptide fingerprints were performed between adult ALL patients and HCs by ClinProtools2.2 software. It was shown that peak number and intensity in serum peptide fingerprints of ND ALL patients were completely different from that of HCs (Figure 1). A total of 33 peptide peaks in the molecular weight range of 1000-10000 Da were significantly different between the two groups (p < 0.05). In ALL ND group, 13 peptides were up-regulated and 20 were down-regulated comparing with healthy controls (Table 1).Figure 1


Serum peptidome based biomarkers searching for monitoring minimal residual disease in adult acute lymphocytic leukemia.

Bai J, He A, Huang C, Yang J, Zhang W, Wang J, Yang Y, Zhang P, Zhang Y, Zhou F - Proteome Sci (2014)

Serum peptide fingerprints and cluster analysis of newly diagnosed ALL and healthy control. A. Comparison of serum peptide fingerprints between ALL patients and healthy controls showed that peak number and intensity of the two groups were completely different. B. Stack view of comparison between ALL patients and healthy controls. (Red: ALL newly diagnosed group Green: Healthy control group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4195909&req=5

Fig1: Serum peptide fingerprints and cluster analysis of newly diagnosed ALL and healthy control. A. Comparison of serum peptide fingerprints between ALL patients and healthy controls showed that peak number and intensity of the two groups were completely different. B. Stack view of comparison between ALL patients and healthy controls. (Red: ALL newly diagnosed group Green: Healthy control group).
Mentions: Despite varying peptide masses and spectrum intensities, the peak coefficient of variations (CVs) were all <14% in the within-run assays and <22% in the between-run assays. The CV value of the relative intensity of each peak in MALDI-TOF-MS was less than 30%, indicating that ClinProt system had good repeatability [25]. To screen serum peptides of interest for adult ALL, comparative analyses of serum peptide fingerprints were performed between adult ALL patients and HCs by ClinProtools2.2 software. It was shown that peak number and intensity in serum peptide fingerprints of ND ALL patients were completely different from that of HCs (Figure 1). A total of 33 peptide peaks in the molecular weight range of 1000-10000 Da were significantly different between the two groups (p < 0.05). In ALL ND group, 13 peptides were up-regulated and 20 were down-regulated comparing with healthy controls (Table 1).Figure 1

Bottom Line: Relative intensities of the five peptides were compared among ALL different groups for the potential importance of MRD evaluation in ALL.Peptides with decreased relative intensities in ND and RR ALL patients were found to be increased in their relative intensities when ALL patients achieved CR.The findings were validated by ELISA and western blot.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, 710004 Shaanxi Province China.

ABSTRACT

Background: The persistence of minimal residual disease (MRD) during therapy is the strongest adverse prognostic factor in acute lymphocytic leukemia (ALL). This study was to identify serum candidate peptides for monitoring MRD in adult ALL.

Results: A total of 33 peptides in the molecular weight range of 1000-10000 Da were detected using ClinProt system and statistically different between adult patients with ALL and healthy controls. Quick classifier (QC) algorithm was used to obtain a diagnostic model consisting of five peptides that could discriminate patients with ALL from controls with a high sensitivity (100%) and specificity (96.67%). The peptides in the QC model were identified as fibrinogen alpha chain (FGA), glutathione S-transferase P1 (GSTP1), isoform 1 of fibrinogen alpha chain precursor, platelet factor 4 (PF4) by high pressure/performance liquid chromatography mass spectrometry/mass spectrometry. Relative intensities of the five peptides were compared among ALL different groups for the potential importance of MRD evaluation in ALL. The peptides with increased relative intensities in newly diagnosed (ND) ALL patients were found to be decreased in their relative intensities after complete remission (CR) of adult ALL. When ALL patients were refractory & relapsed (RR), relative intensities of the peptides were elevated again. Peptides with decreased relative intensities in ND and RR ALL patients were found to be increased in their relative intensities when ALL patients achieved CR. The findings were validated by ELISA and western blot. Further linear regression analyses were performed to eliminate the influence of platelet and white blood cell counts on serum protein contents and indicated that there were no correlations between the contents of all four proteins (PF4, connective tissue active peptide III, FGA and GSTP1) and white blood cell or platelet counts in ALL different groups and healthy control.

Conclusions: We speculate the five peptides, FGA, isoform 1 of fibrinogen alpha chain precursor, GSTP1, PF4 and connective tissue active peptide III would be potential biomarkers for forecasting relapse, monitoring MRD and evaluating therapeutic response in adult ALL.

No MeSH data available.


Related in: MedlinePlus