Angiogenesis in acute promyelocytic leukemia:: induction by vascular endothelial growth factor and inhibition by all-trans retinoic acid

被引:117
作者
Kini, AR
Peterson, LC
Tallman, MS
Lingen, MW
机构
[1] Loyola Univ, Med Ctr, Dept Pathol, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA
[2] Northwestern Univ, Sch Med, Dept Med, Chicago, IL USA
[3] Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL USA
关键词
D O I
10.1182/blood.V97.12.3919
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Recent studies indicate that angiogenesis is important in the pathogenesis of leukemias, apart from its well-established role in solid tumors. In this study, the possible role of angiogenesis in acute promyelocytic leukemia (APL) was explored. Bone marrow trephine biopsies from patients with APL showed significantly increased microvessel density and hot spot density compared with normal control bone marrow biopsies. To identify the mediators of angiogenesis in APL, quantitative and functional assays were performed using the NB4 APL cell line as a model system. Conditioned media (CM) from the NB4 cells strongly stimulated endothelial cell migration. CM from the NB4 cells contained high levels of vascular endothelial growth factor (VEGF) but not basic fibroblast growth factor (bFGF), Most important, the addition of neutralizing VEGF antibodies completely inhibited the ability of NB4 CM to stimulate endothelial cell migration, suggesting that APL angiogenesis is mediated by VEGF. The effect of all-trans retinoic acid (ATRA) on APL angiogenesis was then studied. ATRA therapy resulted in a decrease in bone marrow microvessel density and hot spot density. CM from ATRA-treated APL cells did not stimulate endothelial cell migration. Finally, quantitative assays showed that ATRA treatment resulted in the abrogation of VEGF production by the NB4 cells. These results show that there is increased angiogenesis and VEGF production in APL and that ATRA therapy inhibits VEGF production and suppresses angiogenesis, The addition of specific antiangiogenic agents to differentiation therapy or chemotherapy should be explored.
引用
收藏
页码:3919 / 3924
页数:6
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