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Ángel Hernández‐Hernández

Instituto de Investigación Biomédica de Salamanca

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Marcial Llanillo

Universidad de Salamanca

Fermín Sánchez‐Guijo

Instituto de Investigación Biomédica de Salamanca

Guillermo López-Ruano

Universidad de Salamanca

Rodrigo Prieto-Bermejo

Universidad de Salamanca

Marta Romo-González

Rutgers, The State University of New Jersey

Consuelo del Cañizo

Instituto de Investigación Biomédica de Salamanca

Jesús Sánchez‐Yagüe

Instituto de Investigación Biomédica de Salamanca

Atanasio Pandiella

Centro de Investigación Biomédica en Red de Cáncer

Sara Gutiérrez-Herrero

Instituto de Investigación Biomédica de Salamanca

Carmen Guerrero

Instituto de Investigación Biomédica de Salamanca

Cooperative Institutions

Boston University

134

Seattle University

122

Universidad de Salamanca

Instituto de Investigación Biomédica de Salamanca

Consejo Superior de Investigaciones Científicas

Centro de Investigación del Cáncer

Inserm

Complejo Hospitalario de Salamanca

Centro de Investigación Biomédica en Red de Cáncer

Hudson Institute

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Supplementary Figure 8 from NADPH Oxidases as Therapeutic Targets in Chronic Myelogenous Leukemia

Beatriz Sánchez-Sánchez Sara Gutiérrez-Herrero Guillermo López-Ruano Rodrigo Prieto-Bermejo Marta Romo-González

PDF file - 87KB, Supplementary Figure 8. Inhibitors of NADPH oxidases and Flt3-ITD synergize to prevent the proliferation of two different AML cell lines.

Chronic myelogenous leukemia

10.1158/1078-0432.22452114

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PTPN13 and β-Catenin Regulate the Quiescence of Hematopoietic Stem Cells and Their Interaction with the Bone Marrow Niche

Stem Cell Reports (2015)

Guillermo López-Ruano Rodrigo Prieto-Bermejo Teresa Lopes Ramos Laura San‐Segundo Luis Ignacio Sánchez‐Abarca

The regulation of hematopoietic stem cells (HSCs) depends on the integration of the multiple signals received from the bone marrow niche. We show the relevance of the protein tyrosine phosphatase PTPN13 and β-catenin as intracellular signaling molecules to control HSCs adhesiveness, cell cycling, and quiescence. Lethally irradiated mice transplanted with Lin– bone marrow cells in which PTPN13 or β-catenin had been silenced showed a significant increase of long-term (LT) and short-term (ST) HSCs. A decrease in cycling cells was also found, together with an increase in quiescence. The decreased expression of PTPN13 or β-catenin was linked to the upregulation of several genes coding for integrins and several cadherins, explaining the higher cell adhesiveness. Our data are consistent with the notion that the levels of PTPN13 and β-catenin must be strictly regulated by extracellular signaling to regulate HSC attachment to the niche and the balance between proliferation and quiescence.

Hematopoietic stem cell

10.1016/j.stemcr.2015.08.003

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NOX2 control over energy metabolism plays a role in acute myeloid leukaemia prognosis and survival

Free Radical Biology and Medicine (2023)

Carla Ijurko Marta Romo-González Clara García-Calvo José Luis Sardina Carmen Sánchez‐Bernal

Acute myeloid leukaemia (AML) is a highly heterogeneous disease, however the therapeutic approaches have hardly changed in the last decades. Metabolism rewiring and the enhanced production of reactive oxygen species (ROS) are hallmarks of cancer. A deeper understanding of these features could be instrumental for the development of specific AML-subtypes treatments. NADPH oxidases (NOX), the only cellular system specialised in ROS production, are also involved in leukemic metabolism control. NOX2 shows a variable expression in AML patients, so patients can be classified based on such difference. Here we have analysed whether NOX2 levels are important for AML metabolism control. The lack of NOX2 in AML cells slowdowns basal glycolysis and oxidative phosphorylation (OXPHOS), along with the accumulation of metabolites that feed such routes, and a sharp decrease of glutathione. In addition, we found changes in the expression of 725 genes. Among them, we have discovered a panel of 30 differentially expressed metabolic genes, whose relevance was validated in patients. This panel can segregate AML patients according to CYBB expression, and it can predict patient prognosis and survival. In summary, our data strongly support the relevance of NOX2 for AML metabolism, and highlights the potential of our discoveries in AML prognosis.

Clinical Significance

10.1016/j.freeradbiomed.2023.10.013

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Acetylation and phosphorylation cooperate to regulate the degradation of active GATA-1

Blood Cells Molecules and Diseases (2006)

Ángel Hernández‐Hernández Sergio Ottolenghi Joan Boyes

Degradation

10.1016/j.bcmd.2006.10.021

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Supplementary Figure 3 from NADPH Oxidases as Therapeutic Targets in Chronic Myelogenous Leukemia

Beatriz Sánchez-Sánchez Sara Gutiérrez-Herrero Guillermo López-Ruano Rodrigo Prieto-Bermejo Marta Romo-González

PDF file - 44KB, Supplementary figure 3. Antioxidants and rotenone treatment hamper K562 cell proliferation. DPI treatment reduces BCR-ABL protein levels.

Chronic myelogenous leukemia

K562 cells

breakpoint cluster region

10.1158/1078-0432.22452132

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Supplementary Figure 5 from NADPH Oxidases as Therapeutic Targets in Chronic Myelogenous Leukemia

Beatriz Sánchez-Sánchez Sara Gutiérrez-Herrero Guillermo López-Ruano Rodrigo Prieto-Bermejo Marta Romo-González

PDF file - 340KB, Supplementary figure 5. Combination of NADPH oxidases and BCR-ABL inhibitors progressively increases the proportion of sub-G1 phase cells.

Chronic myelogenous leukemia

breakpoint cluster region

10.1158/1078-0432.22452123

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The DARC-CD82 axis discloses bone marrow macrophages as guardians of long-term hematopoietic stem cells quiescence

Stem Cell Investigation (2016)

Alejandro Pérez‐Fernández Ángel Hernández‐Hernández

In all adult tissues, there is a constant supply of differentiated cells provided by the existence of stem and progenitor cells capable of dividing according to the organism’s demands. One of the most paradigmatic tissues regarding the study of stemness and differentiation is the hematopoietic system. Blood homeostasis is sustained by a subset of cells known as hematopoietic stem and progenitor cells (HSPCs). This is a heterogeneous population that includes from the most immature cells, which have the ability to self-renew and give rise to cells of all blood lineages, to the so-called progenitors, whose differentiation capacity is restricted to a single lineage and display a more limited number of divisions. To date, the main way of distinguishing hematopoietic cells in different stages of maturation has been the use of surface markers based on their restricted or exclusive expression (1). Nevertheless, these markers per se do not show functional characteristics of the cells, since generally only their restricted expression is exploited, but not their biological activity.

10.21037/sci.2016.08.07

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Amphiphilic and hydrophilic nature of sheep and human platelet phosphotyrosine phosphatase forms

Biochimica et Biophysica Acta (BBA) - Biomembranes (1999)

Ángel Hernández‐Hernández Marcial Llanillo M. C. Rodríguez Francisco Pedro Gómez Gómez Jesús Sánchez‐Yagüe

10.1016/s0005-2736(99)00066-8

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Citations (14)

Loss of phosphotyrosine phosphatase activity and changes in the tyrosine phosphorylation state of proteins after storage of sheep platelets in plasma or Seto solution at 4 °C

Vox Sanguinis (2001)

Ángel Hernández‐Hernández Carmen Sánchez‐Bernal M.C. Rodríguez Francisco Pedro Gómez Gómez Marcial Llanillo

Background and Objectives During platelet storage an array of deleterious changes occur, through mechanisms not fully understood, which impair platelet haemostasis. Transfused platelets should maintain the integrated networks of signalling pathways that regulate platelet activation and functionality. We hypothesized that protein phosphorylation and dephosphorylation, which play a fundamental role in these pathways, might be affected by platelet storage. We therefore investigated whether the activity of phosphotyrosine phosphatase (PTP), which belongs to an oxidant‐susceptible group of enzymes involved in the platelet signal‐transduction pathways that ensure platelet functionality, is affected by platelet storage. Materials and Methods Using sheep platelet species as a model system, we conducted serial studies on the membranes of platelets and microparticles shed during platelet storage, in their own plasma or in a synthetic medium called Seto, for up to 5 days at 4 °C. Results A progressive decrease in both total and specific membrane‐associated PTP activities from whole platelets (but not from microparticles) located within each platelet storage bag was observed from day 1 onwards in both types of storage media. These decreases could be partly avoided by the addition of vitamin E. Additionally, the observed decrease in PTP activity was accompanied with increases in the tyrosine phosphorylation of proteins from whole platelets or crude platelet membranes, the tyrosine phosphorylation state of proteins from microparticles remaining basically unchanged. Conclusion Our findings suggest that alterations of at least the tyrosine phosphorylation balance might be one of the reasons for the decrease in the haemostatic function of stored platelets.

10.1046/j.1423-0410.2001.00111.x

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Citations (4)

Comparison of changes in erythrocyte and platelet phospholipid and fatty acid composition and protein oxidation in chronic obstructive pulmonary disease and asthma

Platelets (2007)

Javier de Castro Ángel Hernández‐Hernández Marina Rodríguez José Luis Sardina Marcial Llanillo

Javier De Castroa, Angel Hernández-Hernándezb, Marina C. Rodríguezc, José L. Sardinab, Marcial Llanillob & Jesús Sánchez-Yagüeb*a Radiology Service, Santísima Trinidad Foundation Hospital, Salamanca, Spainb Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca, Spainc Pneumology Service (Neumosalud), Santísima Trinidad Foundation Hospital, Salamanca, Spain

10.1080/09537100600800776

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Citations (44)