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Protein biomarkers distinguish between high- and low-risk pediatric acute lymphoblastic leukemia in a tissue specific manner.

Braoudaki M, Lambrou GI, Vougas K, Karamolegou K, Tsangaris GT, Tzortzatou-Stathopoulou F - J Hematol Oncol (2013)

Bottom Line: Cytogenetic analysis was carried out by G- banding and interphase fluorescent in situ hybridization.Differential proteomic analysis was performed using two-dimensional gel electrophoresis and protein identification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.The differential expression of certain proteins was confirmed by Western blot analysis.

View Article: PubMed Central - HTML - PubMed

Affiliation: First Department of Pediatrics, University of Athens Medical School, Choremeio Research Laboratory, Thivon & Levadias 11527 Goudi-Athens, Greece.

ABSTRACT
The current study evaluated the differential expression detected in the proteomic profiles of low risk- and high risk- ALL pediatric patients to characterize candidate biomarkers related to diagnosis, prognosis and patient targeted therapy. Bone marrow and peripheral blood plasma and cell lysates samples were obtained from pediatric patients with low- (LR) and high-risk (HR) ALL at diagnosis. As controls, non-leukemic pediatric patients were studied. Cytogenetic analysis was carried out by G- banding and interphase fluorescent in situ hybridization. Differential proteomic analysis was performed using two-dimensional gel electrophoresis and protein identification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The differential expression of certain proteins was confirmed by Western blot analysis. The obtained data revealed that CLUS, CERU, APOE, APOA4, APOA1, GELS, S10A9, AMBP, ACTB, CATA and AFAM proteins play a significant role in leukemia prognosis, potentially serving as distinctive biomarkers for leukemia aggressiveness, or as suppressor proteins in HR-ALL cases. In addition, vitronectin and plasminogen probably contributed to leukemogenesis, whilst bicaudal D-related protein 1 could afford a significant biomarker for pediatric ALL therapeutics.

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Scatter plots of Principal Components of protein expression levels. Linear correlations were revealed between the principal components of BMP/LR and BMP/HR patients and BMC, PBC, PBP/HR and PBP/LR. In addition, between BMP/HR and BMP/LR six proteins appeared to distinguish between the stratified patients: AMBP, AFM, GELS, KNG1, CATA and S10A9 (BMP/HR: Bone Marrow Plasma/High Risk, BMC: Bone Marrow Cells, PBC: Peripheral Blood Cells, PBP/HR: Peripheral Blood Plasma/High Risk, PBP/LR: Peripheral Blood Plasma/Low Risk, BMP/LR: Bone Marrow Plasma/Low Risk, ALL: Acute Lymphoblastic Leukemia).
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Figure 6: Scatter plots of Principal Components of protein expression levels. Linear correlations were revealed between the principal components of BMP/LR and BMP/HR patients and BMC, PBC, PBP/HR and PBP/LR. In addition, between BMP/HR and BMP/LR six proteins appeared to distinguish between the stratified patients: AMBP, AFM, GELS, KNG1, CATA and S10A9 (BMP/HR: Bone Marrow Plasma/High Risk, BMC: Bone Marrow Cells, PBC: Peripheral Blood Cells, PBP/HR: Peripheral Blood Plasma/High Risk, PBP/LR: Peripheral Blood Plasma/Low Risk, BMP/LR: Bone Marrow Plasma/Low Risk, ALL: Acute Lymphoblastic Leukemia).

Mentions: Examining the scatters of proteins’ principal components, it was obvious that transformed data manifested a linear behavior between BMP/HR and BMP/LR samples compared to the rest sample groups (Figure 6). This is presented in boxes 25–35 with the exception of boxes 30 and 35, where the difference between BM/LR and BM/HR consists of four proteins. In the rest of the boxes, several proteins differentiate beyond the generalized linear expression pattern, indicating a specific role in leukemia. A magnification of those scatter plots is presented in detail to examine their expression patterns (Figure 7). In total, seven proteins discriminated between LR and HR as well as between the tissue of origin (BM or PB) or cellular components (plasma or cell lysate). These proteins included GELS, S10A9, AMBP, ACTB, CATA, AFM and KNG1 (Additional file 3: Figure S5). The diagrams indicated that the principal components of most proteins could be grouped in a uniform formation, whilst several other proteins emerged as outliers. Subsequently, these proteins might be employed to discriminate between the leukemic cell tissue of origin at diagnosis (BM or PB) or the cellular components (cell lysate or plasma).


Protein biomarkers distinguish between high- and low-risk pediatric acute lymphoblastic leukemia in a tissue specific manner.

Braoudaki M, Lambrou GI, Vougas K, Karamolegou K, Tsangaris GT, Tzortzatou-Stathopoulou F - J Hematol Oncol (2013)

Scatter plots of Principal Components of protein expression levels. Linear correlations were revealed between the principal components of BMP/LR and BMP/HR patients and BMC, PBC, PBP/HR and PBP/LR. In addition, between BMP/HR and BMP/LR six proteins appeared to distinguish between the stratified patients: AMBP, AFM, GELS, KNG1, CATA and S10A9 (BMP/HR: Bone Marrow Plasma/High Risk, BMC: Bone Marrow Cells, PBC: Peripheral Blood Cells, PBP/HR: Peripheral Blood Plasma/High Risk, PBP/LR: Peripheral Blood Plasma/Low Risk, BMP/LR: Bone Marrow Plasma/Low Risk, ALL: Acute Lymphoblastic Leukemia).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3717072&req=5

Figure 6: Scatter plots of Principal Components of protein expression levels. Linear correlations were revealed between the principal components of BMP/LR and BMP/HR patients and BMC, PBC, PBP/HR and PBP/LR. In addition, between BMP/HR and BMP/LR six proteins appeared to distinguish between the stratified patients: AMBP, AFM, GELS, KNG1, CATA and S10A9 (BMP/HR: Bone Marrow Plasma/High Risk, BMC: Bone Marrow Cells, PBC: Peripheral Blood Cells, PBP/HR: Peripheral Blood Plasma/High Risk, PBP/LR: Peripheral Blood Plasma/Low Risk, BMP/LR: Bone Marrow Plasma/Low Risk, ALL: Acute Lymphoblastic Leukemia).
Mentions: Examining the scatters of proteins’ principal components, it was obvious that transformed data manifested a linear behavior between BMP/HR and BMP/LR samples compared to the rest sample groups (Figure 6). This is presented in boxes 25–35 with the exception of boxes 30 and 35, where the difference between BM/LR and BM/HR consists of four proteins. In the rest of the boxes, several proteins differentiate beyond the generalized linear expression pattern, indicating a specific role in leukemia. A magnification of those scatter plots is presented in detail to examine their expression patterns (Figure 7). In total, seven proteins discriminated between LR and HR as well as between the tissue of origin (BM or PB) or cellular components (plasma or cell lysate). These proteins included GELS, S10A9, AMBP, ACTB, CATA, AFM and KNG1 (Additional file 3: Figure S5). The diagrams indicated that the principal components of most proteins could be grouped in a uniform formation, whilst several other proteins emerged as outliers. Subsequently, these proteins might be employed to discriminate between the leukemic cell tissue of origin at diagnosis (BM or PB) or the cellular components (cell lysate or plasma).

Bottom Line: Cytogenetic analysis was carried out by G- banding and interphase fluorescent in situ hybridization.Differential proteomic analysis was performed using two-dimensional gel electrophoresis and protein identification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.The differential expression of certain proteins was confirmed by Western blot analysis.

View Article: PubMed Central - HTML - PubMed

Affiliation: First Department of Pediatrics, University of Athens Medical School, Choremeio Research Laboratory, Thivon & Levadias 11527 Goudi-Athens, Greece.

ABSTRACT
The current study evaluated the differential expression detected in the proteomic profiles of low risk- and high risk- ALL pediatric patients to characterize candidate biomarkers related to diagnosis, prognosis and patient targeted therapy. Bone marrow and peripheral blood plasma and cell lysates samples were obtained from pediatric patients with low- (LR) and high-risk (HR) ALL at diagnosis. As controls, non-leukemic pediatric patients were studied. Cytogenetic analysis was carried out by G- banding and interphase fluorescent in situ hybridization. Differential proteomic analysis was performed using two-dimensional gel electrophoresis and protein identification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The differential expression of certain proteins was confirmed by Western blot analysis. The obtained data revealed that CLUS, CERU, APOE, APOA4, APOA1, GELS, S10A9, AMBP, ACTB, CATA and AFAM proteins play a significant role in leukemia prognosis, potentially serving as distinctive biomarkers for leukemia aggressiveness, or as suppressor proteins in HR-ALL cases. In addition, vitronectin and plasminogen probably contributed to leukemogenesis, whilst bicaudal D-related protein 1 could afford a significant biomarker for pediatric ALL therapeutics.

Show MeSH
Related in: MedlinePlus