NEDD9, an independent good prognostic factor in intermediate-risk acute myeloid leukemia patients

Abstract

Intermediate-risk acute myeloid leukemia (IR-AML) is the largest subgroup of AML patients and is highly heterogeneous. Whereas adverse and favourable risk patients have well-established treatment protocols, IR-AML patients have not. It is, therefore, crucial to find novel factors that stratify this subgroup to implement risk-adapted strategies. The CAS (Crk-associated substrate) adaptor protein family regulates cell proliferation, survival, migration and adhesion. Despite its association with metastatic dissemination and prognosis of different solid tumors, the role of these proteins in hematological malignancies has been scarcely evaluated. Nevertheless, previous work has established an important role for the CAS family members NEDD9 or BCAR1 in the migratory and dissemination capacities of myeloid cells. On this basis, we hypothesized that NEDD9 or BCAR1 expression levels could associate with survival in IR-AML patients and become new prognostic markers. To that purpose, we assessed BCAR1 and NEDD9 gene expression in a cohort of 73 adult AML patients validating the results in an independent cohort (n = 206). We have identified NEDD9, but not BCAR1, as a new a marker for longer overall and disease-free survival, and for lower cumulative incidence of relapse. In summary, NEDD9 gene expression is an independent prognostic factor for favourable prognosis in IR-AML patients.

Keywords: acute myeloid leukemia; bcar1; intermediate-risk; nedd9; prognostic factor.

Figure 1. Survival according to NEDD9 expression in cohorts

Kaplan–Meier curves represent OS of cohort 1 (A) and cohort 2 (B), and DFS of cohort 1 (C) and cohort 2 (D) depending on the NEDD9 expression. Black line and gray line indicate NEDD9 overexpressed and underexpressed, respectively. Log-rank test was used to analyze the statistical significance. P < 0.05 was considered statistically significant (Bold values). OS; Overall survival. DFS; Disease-free survival.

Figure 2. Cumulative incidence of relapse according to NEDD9 expression in cohorts

Kaplan–Meier curves represent CIR of cohort 1 (A) and cohort 2 (B) depending on the NEDD9 expression. Black line and gray line indicate NEDD9 overexpressed and underexpressed, respectively. Gray test for CIR was used to analyze the statistical significance. P < 0.05 was considered statistically significant (Bold values). CIR; Cumulative incidence of relapse.