Acute Leukemia

Acute myeloid leukemia (AML) is an aggressive hematological malignancy associated with a dismal outcome: usually, initial response to therapy is followed by relapse and resistance to therapy. It is therefore necessary to open new therapeutic perspectives aimed at molecular targets.

Reversible phosphorylation is one of the mechanisms that allow the cell to maintain a proper balance between signals that induce and suppress tumors. Hence, the balance between kinases and phosphatases is essential for controlling correct proliferation, apoptosis and differentiation. Many studies have analyzed the abnormal behavior of the kinase proteins in AML; however, the role of phosphatases remains underexplored, despite the fact that they play a key role in controlling cell signaling. Phosphatase protein 2A (PP2A) is a tumor-suppressing protein that has a central regulating function in the cell, where it controls a large variety of functions and signaling pathways. The inactivation of PP2A is an essential event in different types of cancer, which suggests that it may be a highly common and initial alteration in the process of malignant transformation and, therefore, a target with tremendous potential in therapies aimed at activating it. Interestingly, the anticancer activity of several PP2A-activating drugs depends on interaction/sequestration of its endogenous inhibitor SET, an oncogene overexpressed in 28% of AML patients.

Our hypothesis is that the reactivation of PP2A by inhibiting the action of SET on PP2A may be a therapeutic alternative in AML, especially in the subgroup of patients with overexpression of SET, a marker associated with poor outcome in this disease, and that drugs that activate PP2A could be used in combination with specific tyrosine kinase inhibitors, depending on the molecular profile of the patient, or with conventional chemotherapy. Therefore, our lab focuses on the pre-clinical development of novel therapeutics for patients with AML, as well as personalized medicine approaches for these patients. 

Active Projects

  • Discovery and characterization of small molecules that activate the tumor-suppressing protein PP2A for the treatment of acute myeloid leukemia. Spanish Ministry of the Economy and Competitiveness. Carlos III Health Institute (PI14/02073). 2015-2018.

  • Molecular mechanisms in the development and progression of leukemia and lymphoma. Thematic network for cooperative research on cancer (RTICC), of the Carlos III Health Institute. RETICS 2012 call for proposals (RD12/0036/0063). 2013-2016.

The research team forms part of the Healthcare Research Institute of Navarre (IdiSNA) and of the group "Molecular mechanisms in the development and progression of leukemia and lymphoma" of the Thematic Network for Cooperative Research on Cancer (RTICC).

 
  • Desarrollo de nuevas terapias combinadas en la leucemia mieloide aguda. Hacia un tratamiento personalizado en pacientes con sobreexpresión de la oncoproteína SET

    Entidad financiadora: Ministerio de Economía y Competitividad. Instituto de Salud Carlos III (PI17/02272).
    Duración: 2018-2020
    Investigador principal: María D. Odero.

  • Estudio de la oncoproteína SET como diana terapéutica en leucemia mieloide aguda. Hacia un tratamiento personalizado mediante la combinación de activadores de PP2A e inhibidores tirosina quinasas en pacientes con sobreexpresión de SET

    Entidad financiadora: Departamento de Salud del Gobierno de Navarra (29/2015).
    Duración: 2015-2018
    Investigador principal: María D. Odero.

  • Desarrollo de una nueva herramienta para la búsqueda de tratamientos antitumorales más eficaces empleando el modelo animal de pez cebra

    Entidad financiadora: Departamento de Industria del Gobierno de Navarra (0011-1365-2016-000294).
    Duración: 2016-2018
    Investigador principal: María D. Odero.

  • Consorcio CIBER, de la convocatoria 2016 de la Acción Estratégica en Salud 2013-2016 (CIBERONC)

    Entidad financiadora: Instituto de Salud Carlos III (CB16/12/00489).
    Investigador principal: Felipe Prósper.

El equipo de investigación forma parte del Instituto de Investigación Sanitaria de Navarra (IdiSNA) y del grupo CIBERONC (Consorcio CIBER, convocatoria 2016 de la Acción Estratégica en Salud 2013-2016).



Esta Universidad ha recibido una ayuda cofinanciada al 50% por el Fondo Europeo de Desarrollo Regional a través del Programa Operativo FEDER".

"Despite advances in acute myeloid leukemia, the percentage of patients who relapse is very high. Therefore, studies that open new therapeutic perspectives aimed at molecular targets are needed. Our laboratory focuses on the preclinical development of new therapies for patients with AML, with the aim of developing a personalized medicine for these patients", Dra. María D. Odero, Principal Investigator.

More information:

Contact

Contact:
Marisol Ripa
Avda. Pío XII, 55
31008 Pamplona
Spain

(+34) 948 194 700 Ext. 1010
msripa@unav.es

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