High Expression of VAV Gene Family Predicts Poor Prognosis of Acute Myeloid Leukemia

Abstract

Objectives: VAV family genes ( VAV1, VAV2, and VAV3) are associated with prognosis in various cancers; however, they have not been evaluated in acute myeloid leukemia (AML). In this study, the prognostic value of VAV expression in AML was evaluated by a single-center study in combination with bioinformatics analyses. Methods: The expression and prognostic value of VAVs in patients with AML were investigated using various databases, including GEPIA, CCLE, EMBL-EBI, UALCAN, cBioPortal, STRING, and DAVID. Blood samples from 35 patients with AML (non-M3 subtype) and 13 benigh individuals were collected at our center. VAV expression levels were detected by real-time quantitative PCR (RT-qPCR) and western blotting. Clinical data were derived from medical records. Results: Based on data from multiple databases, the expression levels of VAV1, VAV2, and VAV3 were significantly higher in AML than in control tissues ( P < 0.05). RT-qPCR and western blotting results showed that VAV expression in mRNA and protein levels were higher in patients with AML that in the control group ( P < 0.05). Complete remission rates were lower and risks were higher in patients with AML with high VAV1 expression than with low VAV1 expression ( P < 0.05). High levels of VAV2, VAV3, and VAV1 were related to a poor overall survival, and this relationship was significant for VAV1 ( P < 0.05). High expression levels of genes correlated with VAV1, such as SIPA1, SH2D3C, and HMHA1 were also related to a poor prognosis in AML. Functional and pathways enrichment analyses indicated that the contribution of the VAV family to AML may be mediated by the NF-κB, cAMP, and other pathways. Conclusion: VAVs were highly expressed in AML. In particular, VAV1 has prognostic value and is a promising therapeutic target for AML.

Role of Vav1, a hematopoietic signal transduction molecule, as an adaptor protein in health and disease

“…The review focused here on the involvement of Vav1 in hematopoietic malignancies, especially T cell malignancies. High expression of Vav1 was shown to predict a poor prognosis of acute myeloid leukemia (AML) [104]. Also, numerous studies reported missense/deletion mutations (Figure 2A) and fusions/translocations (Figure 2B) in Vav1 in T cell lymphoma (TCL) [105][106][107][108][109].…”

Unraveling the Oncogenic Potential of VAV1 in Human Cancer: Lessons from Mouse Models

“…VAV1 overexpression in hematopoietic malignancies-VAV1 has also been shown to be deregulated in hematologic malignancies [21,[64][65][66]. Thus, it was detected as overexpressed in 13% of B-cell non-Hodgkin Lymphoma (B-NHL) and 34•4% of B-cell chronic lymphocytic leukemia (B-CLL) [64].…”

“…VAV1 overexpression was also associated with activation and higher proliferative activity of diffuse large B-cell lymphoma (DLBCL) [65]. VAV1 expression was also significantly higher in acute myeloid leukemia (AML) patients than in control tissues [66]. Those AML patients with high VAV1 expression were less likely to achieve complete remission compared to those patients with low VAV1 expression, thus suggesting that VAV1 expression levels have prognostic value [66].…”