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Title: Identification of prognostic protein biomarkers in childhood acute lymphoblastic leukemia (ALL)
Authors: Jiang, N.
Kham, S.K.Y.
Koh, G.S.
Suang Lim, J.Y.
Ariffin, H.
Chew, F.T. 
Yeoh, A.E.J.
Keywords: 2-DE
Childhood ALL
Prognostic biomarkers
Issue Date: 16-May-2011
Citation: Jiang, N., Kham, S.K.Y., Koh, G.S., Suang Lim, J.Y., Ariffin, H., Chew, F.T., Yeoh, A.E.J. (2011-05-16). Identification of prognostic protein biomarkers in childhood acute lymphoblastic leukemia (ALL). Journal of Proteomics 74 (6) : 843-857. ScholarBank@NUS Repository.
Abstract: Early response to 7. days of prednisolone (PRED) treatment is one of the important prognostic factors in predicting eventual outcome in childhood acute lymphoblastic leukemia (ALL). Using proteomic tools and clinically important leukemia cell lines (REH, 697, Sup-B15, RS4; 11), we have identified potential prognostic protein biomarkers as well as discovered promising regulators of PRED-induced apoptosis. After treatment with PRED, the four cell lines can be separated into resistant (REH) and sensitive (697, Sup-B15, RS4;11). Two dimensional gel electrophoresis (2-DE) and MALDI-TOF/TOF MS identified 77 and 17 significantly differentially expressed protein spots (p < 0.05) in PRED-sensitive and PRED-resistant cell lines respectively. Several of these were validated by Western blot including proliferating cell nuclear antigen (PCNA), cofilin1, voltage-dependent anion-channel protein1 (VDAC1) and proteasome activator subunit 2 (PA28β). PCNA is a promising protein because of its important roles both in cell cycle regulation and survival control. We subsequently validated PCNA in 43 paired bone marrow samples from children with newly diagnosed ALL (Day 0) and 7. days after PRED treatment (Day 8). ROC curve analysis confirmed that PCNA was highly predictive of PRED response in patients (AUC = 0.81, p = 0.007) and most interestingly, independent of the molecular subtype, providing a promising universal prognostic marker. © 2011 Elsevier B.V.
Source Title: Journal of Proteomics
ISSN: 18743919
DOI: 10.1016/j.jprot.2011.02.034
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