Expression of vascular endothelial growth factor and its receptors FLT-1 and KDR in acute leukemia: Clinical relevance and future prospects

ABSTRACT

Vascular endothelial growth factor [VEGF] and its receptors may play an important role in the pathophysiology of hematopoietic malignancies and the progression of leukemia. The present work aimed to study the expression of VEGF and its receptors namely FLT-1 [VEGFR-1] and KDR/FLK-1 [VEGFR-2] on the transcriptional level in fresh leukemic blast cells isolated from newly diagnosed AML and ALL patients by RT-PCR. The present study demonstrated that acute leukemia whether myeloblastic or lymphoblastic express VEGF and to less extent express its receptors namely FLT-1 and KDR. This may result in the generation of autocrine loop that may support leukemic cell survival and proliferation. On the contrary, to the lack of expression in normal bone marrow samples, VEGF, FLT-1 and KDR were expressed in considerable percentage of the studied AML and ALL patients. There was no significant relationship between the expression of VEGF or its receptors and patients' clinical or laboratory findings. Expression of VEGF and/or KDR receptors was associated with unfavorable treatment outcome and they were associated with risk of treatment failure. This data show that VEGF, FLT-1 and KDR may have clinical relevance and raise the possibility of using angiogenesis inhibitors as a novel therapeutic strategy in acute leukemia. By developing treatment strategies that target both the stromal and tumor compartments, drug resistance may be overcome, and the effect on therapeutic outcome enhanced