Identification of prognostic protein biomarkers in childhood acute lymphoblastic leukemia (ALL).

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), cofilin 1, voltage-dependent anion-channel protein 1 (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.

journal_name

J Proteomics

journal_title

Journal of proteomics

authors

Jiang N,Kham SK,Koh GS,Suang Lim JY,Ariffin H,Chew FT,Yeoh AE

doi

10.1016/j.jprot.2011.02.034

subject

Has Abstract

pub_date

2011-05-16 00:00:00

pages

843-57

issue

6

eissn

1874-3919

issn

1876-7737

pii

S1874-3919(11)00090-X

journal_volume

74

pub_type

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