Disease-specific expression of VEGF and its receptors in AML cells: possible autocrine pathway of VEGF/type1 receptor of VEGF in t(15;17) AML and VEGF/type2 receptor of VEGF in t(8;21) AML

A Hiramatsu; H Miwa; M Shikami; T Ikai; E Tajima; H Yamamoto; N Imai; A Hattori; T Kyo; M Watarai; K Miura; A Satoh; M Itoh; A Imamura; H Mihara; Y Katoh; M Nitta

doi:10.1080/10428190500270386

Disease-specific expression of VEGF and its receptors in AML cells: possible autocrine pathway of VEGF/type1 receptor of VEGF in t(15;17) AML and VEGF/type2 receptor of VEGF in t(8;21) AML

Leuk Lymphoma. 2006 Jan;47(1):89-95. doi: 10.1080/10428190500270386.

Authors

A Hiramatsu¹, H Miwa, M Shikami, T Ikai, E Tajima, H Yamamoto, N Imai, A Hattori, T Kyo, M Watarai, K Miura, A Satoh, M Itoh, A Imamura, H Mihara, Y Katoh, M Nitta

Affiliation

¹ Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan.

PMID: 16465716
DOI: 10.1080/10428190500270386

Abstract

Various angiogenic factors, such as vascular endothelial growth factor (VEGF) and an associated molecule, placenta growth factor (PlGF), are thought to be important for normal and malignant hematopoiesis. This study examined mRNA expression of VEGF, PlGF and receptors for these molecules in AML cells and identified the disease-specific patterns of expression. AML M3 having t(15;17) abnormality showed highest expression of VEGF and VEGF receptor type 1 (VEGFR1), suggesting the autocrine pathway of VEGF-VEGFR1. Then, t(8;21) AML demonstrated augmented expression of VEGF and VEGF receptor type 2 (VEGFR2), suggesting VEGF-VEGFR2 autocrine pathway. Then, addition of VEGFR2 kinase inhibitor in Kasumi-1, a t(8;21) AML cell line, resulted in marked inhibition of cell growth, although growth inhibitory effect of R2 kinase inhibitor to HL-60 was marginal. In addition, cell cycle analysis study showed S-phase cell population reduction by R2 kinase inhibitor in Kasumi-1, but not in HL-60. This observation is thought to be the rationale for novel molecular target therapy directed to angiogenic molecules.

Publication types

Comparative Study

MeSH terms

Adult
Aged
Autocrine Communication / genetics*
Cell Cycle / drug effects
Cell Cycle / physiology
Cell Line, Tumor
Cell Proliferation / drug effects
Chromosome Aberrations
Chromosomes, Human, Pair 15 / genetics
Chromosomes, Human, Pair 17 / genetics
Chromosomes, Human, Pair 21 / genetics
Chromosomes, Human, Pair 8 / genetics
Disease
Enzyme Inhibitors / pharmacology
Gene Expression Regulation, Leukemic / genetics
HL-60 Cells
Humans
Leukemia, Myeloid, Acute / genetics*
Leukemia, Myeloid, Acute / metabolism
Middle Aged
Placenta Growth Factor
Pregnancy Proteins / biosynthesis
Pregnancy Proteins / genetics
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Translocation, Genetic / genetics*
Tumor Cells, Cultured
Vascular Endothelial Growth Factor A / biosynthesis
Vascular Endothelial Growth Factor A / genetics*
Vascular Endothelial Growth Factor Receptor-1 / biosynthesis
Vascular Endothelial Growth Factor Receptor-1 / genetics*
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
Vascular Endothelial Growth Factor Receptor-2 / biosynthesis
Vascular Endothelial Growth Factor Receptor-2 / genetics*

Substances

Enzyme Inhibitors
PGF protein, human
Pregnancy Proteins
RNA, Messenger
Vascular Endothelial Growth Factor A
Placenta Growth Factor
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2