Distinct Biomarker Discovery for Patients with AML
Date Issued
2008
Date
2008
Author(s)
Lee, Cheng-Yeh
Abstract
Acute myeloid leukemia (AML) is a heterogenous clonal disorder of hematopoietic cells. Because AML has high incidence rate and low survival probability among hematopoietic malignancies, it is important to develop biomarkers for clinical diagnosis and prognosis prediction. In the present study, AML biomarkers were estimated from two directions, angiogenesis and stem cell regulation. Bone marrow (BM) plasma from 52 AML patients before chemotherapy and 20 healthy controls were included, and protein concentrations were detected by ELISA. Angiogenesis in BM was thought to correlate with pathogenesis of AML. Vascular endothelial growth factor (VEGF) and angiopoietin (Ang) are the two families involved in the angiogenesis. Seven angiogenic factors were investigated in this study: VEGF-A, VEGF/PlGF, VEGF-C, VEGF-D, Ang-1, Ang-2, and Tie-2. Comparing to normal controls, the marrow levels of VEGF/PlGF, Ang-2, and Tie-2 were significantly higher, and those of VEGF-C and Ang-1 were significantly lower in the AML patients. Thirty-one patients were further subjected to survival analysis. Patients with lower Tie-2 and Ang-2 levels displayed a survival advantage, same as patients with higher VEGF/PlGF and VEGF-D levels. An angio-index [(Ang-2×Tie-2)/(VEGF/PlGF×VEGF-D)] was established. Both survival analysis and Cox regression models revealed that patients with higher angio-index values displayed poor prognosis Osteopontin (OPN) appears to maintain hematopoietic stem cells quiescence in BM niche and to negatively regulate their proliferation and activity. The marrow OPN levels were significantly higher in AML patients than those in healthy controls. Of the 31 patients subjected to survival analysis, those with lower OPN displayed a longer survival time in one-year analysis. Multivariate Cox regression models revealed patients with higher OPN level displayed poor prognosis in both one-year and five-year analysis. As a summary, this study provided good biomarkers for AML diagnosis and prognosis. It also showed new directions for AML biomarker discovery.
Subjects
AML
biomarker
bone marrow
VEGF family
Ang family
osteopontin
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