VEGF-A isoform ratios in Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a cancer of the bone marrow (BM) and blood in which the BM produces abnormal myeloblasts. Vascular Endothelial Growth Factor A (VEGF-A) induces blood vessel formation that contributes to tumor growth, and inhibitors of VEGF-A are used clinically. However cancer cells acquire resistance to these drugs leading to recurrence, so we are exploring alternative pathways that could lead to novel anti-VEGF-A therapeutics. Recent studies using RNA-seq analysis have shown the importance of alternatively spliced isoforms in cancer, particularly those encoding proteins with different functions. With our interest in adult AML we have generated a computational pipeline to analyze RNA-seq databases to compare the isoform expression of VEGF-A in AML BM samples with that in healthy BM samples. We asked whether VEGF-A was highly expressed in AML and whether it’s alternative mRNA splice forms were differentially expressed in leukemia BM cells compared to normal BM cells. We have successfully identified altered VEGF-A isoform expression in adult AML but not pediatric AML. This suggests different cancer processes are prevalent in adult vs pediatric disease and warrants a further examination of other cancer types.