Discovery and identification of
potential biomarkers of pediatric acute lymphoblastic leukemia
BACKGROUND: Acute lymphoblastic leukemia (ALL) is a
common form of cancer in children. Currently, bone marrow biopsy is used for
diagnosis. Noninvasive biomarkers for the early diagnosis of pediatric ALL
are urgently needed. The aim of this study was to discover potential protein
biomarkers for pediatric ALL.
METHODS: Ninety-four pediatric ALL patients and 84 controls
were randomly divided into a "training" set (45 ALL patients, 34
healthy controls) and a test set (49 ALL patients, 30 healthy controls and 30
pediatric acute myeloid leukemia (AML) patients). Serum proteomic profiles
were measured using surface-enhanced laser
desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS). A
classification model was established by Biomarker Pattern Software (BPS).
Candidate protein biomarkers were purified by HPLC, identified by LC-MS/MS
and validated using ProteinChip immunoassays.
RESULTS: A total of 7 protein peaks (9290 m/z, 7769 m/z,
15110 m/z, 7564 m/z, 4469 m/z, 8937 m/z, 8137 m/z) were found with
differential expression levels in the sera of pediatric ALL patients and controls
using SELDI-TOF-MS and then analyzed by BPS to construct a classification
model in the "training" set. The sensitivity and specificity of the
model were found to be 91.8%, and 90.0%, respectively, in the test set. Two
candidate protein peaks (7769 and 9290 m/z) were found to be down-regulated
in ALL patients, where these were identified as platelet factor 4 (PF4) and
pro-platelet basic protein precursor (PBP). Two other candidate protein peaks
(8137 and 8937 m/z) were found up-regulated in the sera of ALL patients, and
these were identified as fragments of the complement component 3a (C3a).
CONCLUSION: Platelet factor (PF4), connective tissue
activating peptide III (CTAP-III) and two fragments of C3a may be potential
protein biomarkers of pediatric ALL and used to distinguish pediatric ALL
patients from healthy controls and pediatric AML patients. Further studies
with additional populations or using pre-diagnostic sera are needed to
confirm the importance of these findings as diagnostic markers of pediatric
ALL.
Shi L. et al. Proteome Sci. 2009 Mar 16;7:7.
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