Abstract
Objective: Neuropilin-1 is a vascular endothelial growth factor receptor that acts as a mediator of angiogenesis. Its importance in hematological malignancies such as acute myeloid leukemia (AML) remains to be elucidated. The aim of this study was to evaluate the significance of neuropilin-1 expression in AML patients by both flow cytometry and real-time polymerase chain reaction (PCR) in regard to its diagnostic and prognostic values. Materials and Methods: Bone marrow aspirates of 44 patients with de novo AML and 12 relapsed AML patients were examined in this study. Ten subjects with nonhematological malignancy serving as the control group were also included. Results: Neuropilin-1 expression by flow cytometry showed a highly significant increase in de novo and relapsed AML patients with a mean of 27.1±17.5% and 21.5±16.6%, respectively, compared to control group’s mean of 3.4±1.9%. A cut-off value of 6% was established as differentiating patients from the control group. By real-time PCR, no statistical significance was found in de novo and relapsed AML patients with a mean of 1.9±3.6 IU/L and 0.3±0.2 IU/L, respectively, compared to the control group’s mean of 0.3±0.1 IU/L. Neuropilin-1 surface expression by flow cytometry showed a significant correlation with total leukocyte count and a negative correlation with hemoglobin level in de novo AML patients. In relapsed AML patients, positive significant correlations were found with age, bone marrow blast percentage, and CD14. Neuropilin-1 mRNA level by real-time PCR showed a positive significant correlation with peripheral blood blast percentage and CD117 and a negative correlation with hemoglobin level in de novo AML patients. In relapsed patients, a positive correlation was found with lactate dehydrogenase. Conclusion: Neuropilin-1 can be used as a tool for diagnosis and prognosis in AML patients. Conflict of interest:None declared.
Highlights
Neuropilins are single-pass transmembrane glycoproteins that were found to be receptors for the vascular endothelial growth factor (VEGF) family of angiogenesis factors, suggesting that the receptor could be involved in blood vessel formation [1,2].VEGF is an important cytokine that contributes to disease evolution in various myeloid neoplasms
Neuropilin-1 can be used as a tool for diagnosis and prognosis in acute myeloid leukemia (AML) patients
A diagnostic cut-off level of NRP-1 percentage expression was detected in this study, discriminating AML patient groups from the healthy control group, and this level was found to be 6% of cells expressing NRP-1 surface antigen
Summary
Neuropilins are single-pass transmembrane glycoproteins that were found to be receptors for the vascular endothelial growth factor (VEGF) family of angiogenesis factors, suggesting that the receptor could be involved in blood vessel formation [1,2].VEGF is an important cytokine that contributes to disease evolution in various myeloid neoplasms. Neuropilins are single-pass transmembrane glycoproteins that were found to be receptors for the vascular endothelial growth factor (VEGF) family of angiogenesis factors, suggesting that the receptor could be involved in blood vessel formation [1,2]. Neuropilin-1 (NRP-1) was found to be a receptor or coreceptor for the specific isoform VEGF165 and expressed on endothelial cells (ECs) and several types of tumor cells. VEGF, as a key factor for angiogenesis and tumor growth, exerts its functions mainly through activation of 2 tyrosine kinase receptors: VEGFR-1 (Flt 1) and VEGFR-2 (KDR). Unlike Flt 1 and KDR, NRP-1 does not possess intrinsic tyrosine kinase activity and forms a complex with KDR to transmit signals of VEGF. When co-expressed with KDR on ECs, NRP-1 promotes the binding of VEGF165 to KDR and enhances VEGF-mediated mitogenic and chemotactic activity [3]
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