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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

MS/MS map of peptide with MW of 7764.29 Da. A. The enlarged picture of peptide with MW of 7764.29 Da. B. The b and y ions spectra are used to identify the peptide with MW of 7764.29 Da. C. The sequence of the peptide with MW of 7764.29 Da.
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Fig7: MS/MS map of peptide with MW of 7764.29 Da. A. The enlarged picture of peptide with MW of 7764.29 Da. B. The b and y ions spectra are used to identify the peptide with MW of 7764.29 Da. C. The sequence of the peptide with MW of 7764.29 Da.

Mentions: The peptides in the QC model were purified and identified by HPLC-MS/MS. Data analysis software BioworksBrowser 3.3.1 SP1 was applied for Sequest™ searching. Positive protein identification was accepted for a peptide with Xcorr of greater than or equal to 3.50 for triply charged ions and 2.5 for doubly charged ions, and all with ΔCn ≥ 0.1, peptide probability ≤ 1e-3. Peptides with molecular weight of 2661.27 Da, 2991.46 Da, 3443.92 Da and 7764.29 Da were identified as peptide fragments of fibrinogen alpha chain, glutathione S-transferase P1, isoform 1 of fibrinogen alpha chain precursor 1 and platelet factor 4 (Table 2, Figures 4, 5, 6 and 7). However, peptide with molecular weight of 9288.31 Da was not identified because of high molecular weight. Literature review suggested that it might be the connective tissue active peptide III [18,27].Table 2


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)

MS/MS map of peptide with MW of 7764.29 Da. A. The enlarged picture of peptide with MW of 7764.29 Da. B. The b and y ions spectra are used to identify the peptide with MW of 7764.29 Da. C. The sequence of the peptide with MW of 7764.29 Da.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig7: MS/MS map of peptide with MW of 7764.29 Da. A. The enlarged picture of peptide with MW of 7764.29 Da. B. The b and y ions spectra are used to identify the peptide with MW of 7764.29 Da. C. The sequence of the peptide with MW of 7764.29 Da.
Mentions: The peptides in the QC model were purified and identified by HPLC-MS/MS. Data analysis software BioworksBrowser 3.3.1 SP1 was applied for Sequest™ searching. Positive protein identification was accepted for a peptide with Xcorr of greater than or equal to 3.50 for triply charged ions and 2.5 for doubly charged ions, and all with ΔCn ≥ 0.1, peptide probability ≤ 1e-3. Peptides with molecular weight of 2661.27 Da, 2991.46 Da, 3443.92 Da and 7764.29 Da were identified as peptide fragments of fibrinogen alpha chain, glutathione S-transferase P1, isoform 1 of fibrinogen alpha chain precursor 1 and platelet factor 4 (Table 2, Figures 4, 5, 6 and 7). However, peptide with molecular weight of 9288.31 Da was not identified because of high molecular weight. Literature review suggested that it might be the connective tissue active peptide III [18,27].Table 2

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