Abstract
Angiogenic factors play an essential role in normal and pathologic angiogenesis, but their clinical role in acute myeloid leukemia (AML) remains unclear. We investigated the expression of Ang-1, Ang-2, Tie2, VEGF-A, and VEGF-C genes in bone marrow (BM) mononuclear cells by real-time quantitative PCR (RQ-PCR) in a cohort of 126 patients with newly diagnosed de novo AML and normal marrow donors. Here we show that high pre-treatment levels of Ang-2 in the BM indicate an unfavorable prognosis in AML. Only karyotype (hazard ratio 2.19, 95% CI 1.25-3.42, P=0.005) and expression of Ang-2 (hazard ratio 2.05, 95% CI 1.20-3.52, P=0.009), but not other angiogenic factors, were independent prognostic factors for overall survival by multivariate analysis. The prognostic significance of Ang-2 expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics. Subgroup analysis showed that Ang-2 expression had prognostic impact on patients with low (but not high) Ang-1 or Tie2 levels, and on patients with high (but not low) VEGF-A or VEGF-C levels.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Aged, 80 and over
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Angiopoietin-1 / genetics*
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Angiopoietin-1 / metabolism
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Angiopoietin-2 / genetics*
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Angiopoietin-2 / metabolism
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Bone Marrow / metabolism
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Cohort Studies
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DNA Primers / chemistry
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Enzyme-Linked Immunosorbent Assay
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Female
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Gene Expression Regulation, Leukemic / physiology*
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Humans
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Immunoenzyme Techniques
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Leukemia, Myeloid, Acute / classification
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Leukemia, Myeloid, Acute / genetics*
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Leukemia, Myeloid, Acute / metabolism
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Male
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Middle Aged
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Prognosis
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptor, TIE-2 / genetics*
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Receptor, TIE-2 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Survival Rate
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Vascular Endothelial Growth Factor A / genetics*
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Vascular Endothelial Growth Factor A / metabolism
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Vascular Endothelial Growth Factor C / genetics*
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Vascular Endothelial Growth Factor C / metabolism
Substances
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ANGPT1 protein, human
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Angiopoietin-1
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Angiopoietin-2
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DNA Primers
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RNA, Messenger
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factor C
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Receptor, TIE-2