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Projects. Life and Earth Sciences

Oxidise NADPH and the regulation of intermediate leukemic cell metabolism: the search for new therapeutic strategie

Lead Researcher:
Ángel Hernández Hernández

Research Centre:
Instituto de Investigación Biomédica de Salamanca (IBSAL). CSIC-Universidad de Salamanca.

Abstract: 

Ángel Hernández HernándezTumour cells, even when sufficient oxygen is present, use glucose fermentation into lactate to obtain energy, which is traditionally known as the "Warburg effect". Glutamine dependency and excessive production of substances that react with oxygen (ROS) are other signs of oncometabolic identity. Chronic myeloidleukaemia (CML) is caused by the expression of BCR-ABL oncogenic kinase. Some studies suggest that BCR-ABL affect glucose metabolism and increase levels of intracellular ROS, partially through oxidase NADPH. Our working hypothesis is that the over-production of ROS in tumoral cells may be considered to be one more aspect of their particular metabolic adaptation. We recently showed that oxidase NADPH are an interesting therapeutic target against CML, given that these enzymes help keep the BCR-ABL signalling pathway active.

The simultaneous inhibition of BCR-ABL and oxidase NADPH is highly synergic. Our results suggest that the same strategy could be applied to acute myeloidleukaemia (AML). Given these precedents, we are interested in studying the involvement of oxidase NADPH in the regulation of leukaemia cell metabolism. This would give rise to the development of new therapies targeting cell metabolism, in combination with NADPH oxidase inhibitors and/or inhibitors of BCR-ABL and FLT3-ITD oncokinases, which may be of interest for the treatment of CML or AML, and may also be useful as a model for other types of oncokinase-governed tumours or those in which oxidase NADPH are involved.


Researcher's web address:



Ángel Hernández Hernández

Graduate (1993) and Doctor in Biology (1998) from the University of Salamanca. Extraordinary prize for Degree and Doctorate. Postdoctoral visits in the Instituto Cajal (Madrid, 1998-2000) and the Institute of Cancer Research (ICR, London, 2000-2003). Research visits in other prestigious international centres such as the Karolinska Institute (Huddinge, Sweden) and the Molecular Pathology Institute (IMP, Vienna). Professor in the University of Salamanca from 2008, and group leader in cancer of the Instituto de Investigación Biomédica de Salamanca-IBSAL. Laboratory research centres on analysing the role of oxygen-reactive substances (ORS) as secondary messengers during haematopoiesis. Tumour cells present high levels of ORS, and our work shows that oxidase NADPH, a family of enzymes that specialise in the production of ORS, are an interesting therapeutic target against leukaemia, so that we are interested in exploring the study of this enzyme family. The scientific career of Dr. Hernández Hernández is backed by his direction of several theses, as well as publications in highly prestigious journals such as Mol Cell Biol., EMBO J., Cell Death Differ. and Clin Cancer Res, among others.


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