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.
Highlights
Acute myeloid leukemia (AML) is a heterogeneous group of diseases characterized by the infiltration of bone marrow, blood, and other tissues by proliferative, clonal and abnormally differentiated immature cells of the hematopoietic system [1,2,3].According to cytogenetic and molecular features, AML patients are classified into favorable, intermediate, or adverse risk groups and their therapy after remission are riskwww.impactjournals.com/oncotarget adapted [2]
In Cohort 1, the median of white blood cells (WBC) count, the percentage of patients with the WBC count over 20 × 109/L, Fms-related tyrosine kinase 3 (FLT3)/ITD+ and CCAAT/enhancer-binding protein alpha (CEBPA)- were significantly higher than in Cohort 2
A remarkable proportion of patients included in the intermediate-risk cytogenetics group show diverse outcome
Summary
Acute myeloid leukemia (AML) is a heterogeneous group of diseases characterized by the infiltration of bone marrow, blood, and other tissues by proliferative, clonal and abnormally differentiated immature cells of the hematopoietic system [1,2,3].According to cytogenetic and molecular features, AML patients are classified into favorable, intermediate, or adverse risk groups and their therapy after remission are riskwww.impactjournals.com/oncotarget adapted [2]. In contrast to established treatment protocols for patients in the favorable and adverse risk groups, the clinical decision guideline for the IR-AML group remains unclear [4]. Mutations of RUNX1, ASXL1 and TP53 have been associated with adverse outcome and are included in the standard diagnosis [4] Additional molecular factors, such as IDH1, IDH2, TET2, DNMT3A, MLL-PTD or NRAS, have demonstrated capacity to stratify a subset of IR-AML patients, allocating to them into the good or poor prognosis groups [12, 13]; they have not been introduced in clinical practice yet; the need still remains to identify new prognostic indicators with higher stratification capacity
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