Oncotarget

Research Papers:

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

Victor Pallarès, Montserrat Hoyos, M. Carmen Chillón, Eva Barragán, M. Isabel Prieto Conde, Marta Llop, María Virtudes Céspedes, Josep F. Nomdedeu, Salut Brunet, Miguel Ángel Sanz, Marcos González-Díaz, Jorge Sierra, Isolda Casanova and Ramon Mangues _

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Oncotarget. 2017; 8:76003-76014. https://doi.org/10.18632/oncotarget.18537

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Abstract

Victor Pallarès1,2, Montserrat Hoyos1,2, M. Carmen Chillón3,8, Eva Barragán4,8, M. Isabel Prieto Conde 3, Marta Llop4, María Virtudes Céspedes1,5, Josep F. Nomdedeu2, Salut Brunet2, Miguel Ángel Sanz4,8, Marcos González-Díaz3,8, Jorge Sierra2,6,7,#, Isolda Casanova1,5,6,* and Ramon Mangues1,5,6,*,#

1Biomedical Research Institute Sant Pau (IIB Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

2Department of Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

3Department of Hematology, University Hospital of Salamanca and Center of Investigation in Cancer-IBMCC, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain

4Clinical Laboratory and Department of Hematology, University Hospital La Fe, Valencia, Spain

5CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain

6Josep Carreras Leukemia Research Institute, Barcelona, Spain

7Universitat Autònoma de Barcelona, Barcelona, Spain

8CIBER in Oncology (CIBER-ONC), Madrid, Spain

*These authors contributed equally to this work as senior authors

#These authors contributed equally as corresponding authors

Correspondence to:

Ramon Mangues, email: [email protected]

Jorge Sierra, email: [email protected]

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

Received: December 15, 2016     Accepted: June 02, 2017     Published: June 16, 2017

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.


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