Gene Expression of VEGF-A and VEGF-C in Peripheral Blood Mononuclear Cells of Iranian Patients with Acute Myeloid Leukemia.

Abstract

The crucial role of angiogenesis in the pathophysiology of acute myeloid leukemia (AML) has been proposed. One of the key regulators of angiogenesis is the vascular endothelial growth factor (VEGF). Among the VEGF family, it has been observed that VEGF-A and VEGF-C are expressed by AML cells and mediate leukemic cell proliferation, survival, and resistance to chemotherapy. Emerging evidence, however, suggests that elevated levels of VEGF or a proangiogenic phenotype may impede, rather than promote, early tumor development and progression. As the significance of VEGF-A and VEGF-C levels in the pathogenesis of AML has not been clarified well, the aim of this study is to evaluate gene expression of these angiogenesis promoters and its possible prognostic value in peripheral blood mononuclear cells of Iranian patients with AML.We investigated the mRNA expression of VEGF-A and VEGF-C in peripheral blood mononuclear cells of 27 patients with newly diagnosed AML and 28 healthy controls by quantitative real-time PCR.Expression of VEGF-C mRNA was significantly lower in AML patients than in healthy controls (p<0.001). However, there was no significant decrement in expression of VEGF-A mRNA of AML patients compared to the control group (p=0.861). VEGF-A and VEGF-C expression were not able to predict clinical outcome.Our data showed that AML is associated with a decreased expression of VEGF-C mRNA. However, expression levels did not influence the clinical outcome in our study. It seems that angiogenesis is affected by different cytokines other than VEGF-C or VEGF-A, and VEGF is also affected by different cytokines. Taken together, these findings help to provide new insights into the investigation of other angiogenic factors and cytokines that may play roles in the pathogenesis of AML.None declared.Amaç: Akut miyeloid l?semi (AML) patofizyolojisinde anjiyogenezin?nemli rol oynad??? ileri sأ¼rأ¼lmektedir. Anjiyogenezdeki anahtar dأ¼zenleyicilerden biri damar endotel bأ¼yأ¼me fakt?rأ¼- vascular endothelial growth factor (VEGF)- dأ¼r. VEGF ailesi içinde, VEGF-A ve VEGF-C'nin AML hأ¼creleri taraf?ndan eksprese edildi?i ve l?semik hأ¼crenin proliferasyonu, ya?am? ve kemoterapiye direncine arac? oldu?u g?zlenmi?tir. Buna ra?men mevcut bilgiler, artm?? VEGF dأ¼zeylerinin veya proanjiyogenik bir fenotipin erken tأ¼m?r geli?imi ve progresyonunu tetiklemekten ziyade engelleyebildi?ini g?stermi?tir. VEGF-A ve VEGF-C dأ¼zeylerinin AML patogenezindeki yeri tam olarak aç?klanamad???ndan, bu çal??man?n amac? ?ranl? AML hastalar?n?n periferik kan mononأ¼kleer hأ¼crelerinde s?zأ¼geçen anjiyogenez dأ¼zenleyicilerinin gen ekspresyonlar?n? ve prognostik de?erini incelemektir.Gereç ve Y?ntemler: Yirmi yedi yeni tan? AML hastas? ile 28 sa?l?kl? k?ntrolأ¼n periferik kan mononأ¼kleer hأ¼crelerinde kantitatif real-time PCR ile VEGF-A ve VEGF-C'nin mRNA ekspresyonu ara?t?rd?k.Bulgular: AML hastalar?ndaki VEGF-C mRNA ekspresyonu sa?l?kl? kontrollere g?re belirgin olarak dأ¼?أ¼ktأ¼ (p<0.001). Buna kar??l?k VEGF-A mRNA ekspresyonunda kontrol grubuna g?re anlaml? bir azalma yoktu (p=0.861). VEGF-A ve VEGF-C ekspresyonunun klinik sonucu ?n g?rme kapasitesi yoktur.Sonuç: Bulgular?m?z AML'nin azalm?? VEGF-C mRNA ekspresyonu ile ili?kili oldu?unu g?sterdi. Buna ra?men ekspresyon dأ¼zeyleri bizim çal??mam?zda klinik sonucu etkilemedi. Hem VEGF ba?ka sitokinlerden hem de anjiyogenez VEGF-C veya VEGF-A'dan ba?ka sitokinlerden etkileniyor gibi g?rأ¼nmektedir. Sonuç olarak, bulgular?m?z AML patogenezinde rolأ¼ olabilecek di?er anjiyojenik fakt?r ve sitokinlerin ara?t?r?lmas?na yeni bir bak?? aç?s? sa?layarak yard?mc? olacakt?r.