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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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Representative gel images of BM plasma derived from LR- (A), HR-ALL (B) and non-leukemic (C) patients. The differentially expressed spots are annotated and indicated by arrows.
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Figure 1: Representative gel images of BM plasma derived from LR- (A), HR-ALL (B) and non-leukemic (C) patients. The differentially expressed spots are annotated and indicated by arrows.

Mentions: A mean of 361 ± 22 spots per gel were compared between BM plasma samples and controls and in total 46 proteins were found to be differentially expressed; 18 proteins in HR-ALL patients and 16 in LR-ALL patients (Figure 1). Among them, there were six proteins worth mentioning [ceruloplasmin (CERU), clusterin (CLUS), prothrombin (THRB), alpha-1-microglobulin/bikunin precursor (AMBP), vitamin D-binding protein (VTDB) and ficolin-3 (FCN3)], which were found up-regulated and a further two gelsolin (GELS) and protein S100-A9 (S10A9) found down-regulated in BM plasma derived from HR-ALL patients. Regarding the most considerable proteins identified in BM plasma from LR-patients, VTDB and kininogen-1 (KNG1) were found overexpressed, whilst S10A9 and afamin (AFAM) were significantly down-regulated. Importantly, KNG1 was found significantly up-regulated in the LR-ALL group of patients when compared to the HR-ALL. Overall, twelve proteins were found differentially expressed in ALL patients, independently of the risk them, GELS, KNG1, CD5 antigen (CD5L), leucine-rich alpha-2-glycoprotein precursor (A2GL), vitronectin (VTNC) and Ig mu chain C region (IGHM) were down-regulated, whereas increased expression of ZA2G, VTDB, TRFE, plasminogen (PLMN), alpha-2-macroglobulin (A2MG) and AMBP was detected. The expression level of all these proteins was altered significantly (Additional file 2: Table S1).


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)

Representative gel images of BM plasma derived from LR- (A), HR-ALL (B) and non-leukemic (C) patients. The differentially expressed spots are annotated and indicated by arrows.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Representative gel images of BM plasma derived from LR- (A), HR-ALL (B) and non-leukemic (C) patients. The differentially expressed spots are annotated and indicated by arrows.
Mentions: A mean of 361 ± 22 spots per gel were compared between BM plasma samples and controls and in total 46 proteins were found to be differentially expressed; 18 proteins in HR-ALL patients and 16 in LR-ALL patients (Figure 1). Among them, there were six proteins worth mentioning [ceruloplasmin (CERU), clusterin (CLUS), prothrombin (THRB), alpha-1-microglobulin/bikunin precursor (AMBP), vitamin D-binding protein (VTDB) and ficolin-3 (FCN3)], which were found up-regulated and a further two gelsolin (GELS) and protein S100-A9 (S10A9) found down-regulated in BM plasma derived from HR-ALL patients. Regarding the most considerable proteins identified in BM plasma from LR-patients, VTDB and kininogen-1 (KNG1) were found overexpressed, whilst S10A9 and afamin (AFAM) were significantly down-regulated. Importantly, KNG1 was found significantly up-regulated in the LR-ALL group of patients when compared to the HR-ALL. Overall, twelve proteins were found differentially expressed in ALL patients, independently of the risk them, GELS, KNG1, CD5 antigen (CD5L), leucine-rich alpha-2-glycoprotein precursor (A2GL), vitronectin (VTNC) and Ig mu chain C region (IGHM) were down-regulated, whereas increased expression of ZA2G, VTDB, TRFE, plasminogen (PLMN), alpha-2-macroglobulin (A2MG) and AMBP was detected. The expression level of all these proteins was altered significantly (Additional file 2: Table S1).

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