-
Cuminetti, Vincent & Arranz, Lorena
(2024).
Succinate receptor 1 signaling regulates hematopoiesis via S100/a8 and S100/a9 in health and malignancy.
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Cuminetti, Vincent; Konieczny, Joanna; Bernal Mera, Aurora; Ferre Oliver, Marc; Gomez, Manuel José & Vilaplana-Lopera, Nuria
[Show all 18 contributors for this article]
(2024).
Succinate receptor 1 signaling regulates hematopoiesis via S100/a8 and S100/a9 in health and malignancy.
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Ferré, Marc & Arranz, Lorena
(2023).
Exploring the transformation potential of haematopoietic stem cells under germinal NTRK1 mutations.
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Cuminetti, Vincent & Arranz, Lorena
(2023).
Succinate receptor 1 signaling regulates hematopoiesis in health and malignancy.
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Cuminetti, Vincent & Arranz, Lorena
(2023).
Succinate receptor 1 signaling regulates hematopoiesis in health and malignancy.
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Arranz, Lorena & Stranden, Anne Lise
(2023).
Norwegian discovery gives hope for blood cancer patients.
[Internet].
https://www.sciencenorway.no/.
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Arranz, Lorena & Rasmussen, Nikoline Lander
(2023).
NCMM Associate Investigator collaboration leads to important findings on the development of acute myeloid leukemia.
[Internet].
https://www.med.uio.no/ncmm/.
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Arranz, Lorena & Stranden, Anne Lise
(2023).
Norsk funn gir håp for blodkreftpasienter.
[Internet].
https://www.forskning.no/.
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Arranz, Lorena & Bludd, Ellen Kathrine
(2023).
Leukemipasienter kan få hjelp av ny metode.
[Internet].
https://uit.no/nyheter/artikkel?p_document_id=800155.
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Villatoro Gonzalez, Alicia Elena; Cuminetti, Vincent; Bernal Mera, Aurora; Torroja, Carlos; Cossío, Itziar & Benguría, Alberto
[Show all 22 contributors for this article]
(2023).
Author Correction: Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation (Nature Communications, (2023), 14, 1, (12), 10.1038/s41467-022-35700-9).
Nature Communications.
ISSN 2041-1723.
14(1).
doi:
10.1038/s41467-023-39601-3.
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Arranz, Lorena
(2022).
Targeting stem cells and their niches in myeloid malignancies.
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Cuminetti, Vincent & Arranz, Lorena
(2022).
Disruption of succinate receptor signaling promotes myeloproliferation and acute myeloid leukaemia.
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Arranz, Lorena
(2022).
Therapeutic targeting of stem cells and their niches in myeloid malignancies.
Show summary
Long life expectancy is resulting in aged societies and a remarkable increase in age-related diseases, including cancer. Stem cells self-renew and provide the source for replenishing mature cells in the organism throughout its life. These fascinating abilities ensure tissue regeneration, but must be fine-tuned regulated as their imbalance may contribute to both, ageing and cancer. Stem cell behaviour results from integration of cell-autonomous signals and extracellular cues received from the stem cell niche. Our research interest focusses on these processes that control stem cell behaviour. Taking the hematopoietic system as the primary model, my group aims at understanding the mechanisms contributing to stem cell malignant transformation using an integrative perspective that considers cell-autonomous alterations in the stem cell and remodeling of the stem cell niche. We will present unpublished observations on the role of inflammation and signaling oncometabolites in myeloid leukaemias. Our goal is the identification of novel therapeutic targets of clinical interest that will help improve survival rates and quality of life in patients of haematological malignancies.
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Arranz, Lorena
(2022).
Pathophysiology of stem cells.
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-
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Arranz, Lorena
(2021).
Cancer Stem Cells in Hematological Cancers.
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Arranz, Lorena
(2021).
Stem cells and their niche as a basis for future therapies.
-
Arranz, Lorena
(2021).
Targeting stem cells and their niches in myeloid malignancies.
-
Arranz, Lorena
(2021).
Targeting the stem cell niche in myeloid malignancies.
-
Arranz, Lorena
(2021).
Endogenous IL-1 receptor antagonist
represses myelopoiesis and guards against leukemia.
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Arranz, Lorena
(2021).
Therapeutic targeting of stem cells and their niches in disease: A focus on myeloid malignancies.
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Arranz, Lorena
(2020).
Stem cells and their niche as a basis for future therapies.
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Arranz, Lorena
(2020).
Targeting the stem cell niche in myeloid malignancies.
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Arranz, Lorena
(2019).
Imbalance of IL-1β signaling over IL-1 receptor antagonist favors myeloid output and promotes malignancy in leukemia.
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Bernal, Aurora & Arranz, Lorena
(2019).
Bone marrow neuropathy in acute myeloid leukemia.
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Cuminetti, Vincent & Arranz, Lorena
(2019).
Investigating the role of succinate receptor 1 as regulator of steady-state and malignant hematopoeisis.
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Arranz, Lorena
(2019).
IL-1 receptor antagonist prevents IL-1β-induced myeloid bias in hematopoietic stem cells and protects from leukemia.
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Cuenca-Zamora, EJ; Ruiz-Pividal, JF; Zamora-Plana, L; Bellosino, B; De la Morena-Barrio, ME & Bohdan, N
[Show all 15 contributors for this article]
(2019).
THE GERMINAL VARIANTS RS6336/RS6339 OF NTRK1 PREDISPOSE TO CHRONIC MYELOPROLIFERATIVE NEOPLASIAS.
Haematologica.
ISSN 0390-6078.
104,
p. 59–60.
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Arranz, Lorena
(2018).
Stem Cells, Aging and Cancer @ UiT.
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Bernal, Aurora; Konieczny, Joanna; Villatoro, Alicia & Arranz, Lorena
(2018).
DOES AGING FOSTER TRANSFORMATION TO ACUTE MYELOID LEUKAEMIA?
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Villatoro, Alicia & Arranz, Lorena
(2018).
Anti-inflammatory properties of the bone marrow in leukemic transformation.
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Arranz, Lorena
(2018).
Novel regulatory networks of hematopoiesis in health and disease.
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Arranz, Lorena
(2018).
El nicho medular y la inflamacion en las NMP.
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Arranz, Lorena
(2018).
Novel Regulatory Network of Haematopoiesis in Acute Myeloid Leukaemia.
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Ho, Ya-Hsuan; del Toro, Raquel; Rivera-Torres, Jose; Rak, Justyna; Korn, Claudia & García-García, Andrés
[Show all 23 contributors for this article]
(2018).
Aging of Bone Marrow Microenvironment Promotes Myeloid Bias of Hematopoietic Progenitors and Is a Target in Age-Related Myeloproliferative Neoplasms.
Blood.
ISSN 0006-4971.
132,
p. 3842–3842.
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Arranz, Lorena
(2017).
Stem Cells, Aging and Cancer at UiT.
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Bernal, Aurora; Serulla, Marc; Villatoro, Alicia & Arranz, Lorena
(2017).
NEUROGLIAL REGULATION OF THE HEMATOPOIETIC STEM CELL NICHE IN ACUTE MYELOID LEUKEMIA.
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Arranz, Lorena
(2017).
Role for the Stem Cell Niche in Myeloid Neoplasias.
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Grimolizzi, Franco; Villatoro, Alicia & Arranz, Lorena
(2017).
Oncometabolite succinate in acute myeloid leukemia.
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Villatoro, Alicia; Bernal, Aurora; Grimolizzi, Franco; Tello, Almudena; Konieczny, Joanna & Arranz, Lorena
(2017).
IL-1 receptor antagonist participates in hematopoietic stem cell differentiation.
Show summary
Hematopoietic stem cells (HSCs) are in charge of blood cell production and reside in the bone marrow, where their function is regulated by external signals. Interleukin 1β (IL-1β) is an inflammatory mediator that drives HSC differentiation into the myeloid lineage, and enhanced IL-1β signaling plays a key role in hematological malignancies. Here, we identified a critical role of the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1rn) on HSC differentiation in vivo. IL-1rn binds to IL-1 receptor 1 (IL-1R1) in competition with both IL-1β and IL-1α, and impedes their function. Abrogation of IL-1rn has no impact on HSC survival or proliferation, but biases HSC differentiation into the myeloid lineage whilst hampering lymphoid development. The output is bone marrow hypercellularity and increased circulating white blood cells. The stromal compartment of the bone marrow is damaged as shown by reduced numbers of mesenchymal stem cells and incipient fibrosis. We are currently investigating the underlying molecular mechanisms and cell subsets that participate in these processes. Our data suggest that defects in IL-1rn may participate in hematological disease development, and point to this pathway as a good candidate for therapeutic interventions.
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Bernal, Aurora; Serulla, Marc; Villatoro, Alicia; Gargiulo, Ernesto & Arranz, Lorena
(2017).
Neuroglial Regulation of the Hematopoietic Stem Cell Niche in Acute Myeloid Leukemia.
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Arranz, Lorena
(2017).
Role for the Stem Cell Niche in Myeloid Neoplasias.
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Arranz, Lorena
(2017).
Role for the Stem Cell Niche in Myeloid Neoplasias.
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Arranz, Lorena & Øvreberg, Elisabeth
(2017).
Stor pengegave til kreftforskningen ved UiT.
[Internet].
https://uit.no/.
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Arranz, Lorena
(2017).
Welcome to Lorena Arranz from University of Tromsø (UiT).
[Internet].
https://www.med.uio.no/ncmm/.
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Arranz, Lorena
(2016).
Stem Cell Aging and Cancer at UiT.
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Gargiulo, Ernesto; Villatoro, Alicia; Eliassen, Liv Tone & Arranz, Lorena
(2016).
Succinate regulation of haematopoietic stem cells in health and malignancy.
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Arranz, Lorena
(2016).
Stem Cell Aging and Cancer Research Group at the Department of Medical Biology
.
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Arranz, Lorena
(2016).
Novel regulatory mechanisms of haematopoietic stem cells in health and disease.
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Arranz, Lorena
(2016).
Novel HSC regulatory mechanisms in AML development and targeting.
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Arranz, Lorena
(2016).
A Role for the Stem Cell Niche in Myeloid Leukemias?
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Arranz, Lorena
(2015).
Stem Cell Aging and Cancer at UiT.
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Arranz, Lorena
(2015).
Neuropathy of the haematopoetic stem cell niche is essential for myeloproliferative neoplasms.
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Arranz, Lorena
(2015).
Neuropathy of the haematopoietic stem cell niche is essential for myeloproliferative neoplasms.
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Arranz, Lorena
(2015).
Neuroglial Dysregulation of the Haematopoietic Stem Cell Niche in Myeloid Leukaemias.
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Arranz, Lorena & Myreng, Jørn K
(2015).
Håper på færre bivirkninger i kreft-behandlingen.
[Newspaper].
https://www.itromso.no/nyheter/i/zrv9W1/haper-pa-faerre-bivi.
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Arranz, Lorena & Mackenroth, Anika
(2015).
Det er kreftforskerne som sitter med våpnene.
[Internet].
https://uit.no/nyheter/artikkel?p_document_id=438228.
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Arranz, Lorena & Øvreberg, Elisabeth
(2015).
Vil bli en ressurs på stamcelleforskning.
[Internet].
https://uit.no/nyheter/artikkel?p_document_id=423873&p_dim.
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Arranz, Lorena
(2014).
Presentation of our new research group.
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Villatoro, Alicia & Arranz, Lorena
(2022).
The role of interleukin-1 receptor antagonist in normal and malignant hematopoiesis.
UiT Norges arktiske universitet.
Show summary
Interleukin-1β (IL-1β) is a pleiotropic inflammatory cytokine that exerts multiple roles in both physiological and pathological conditions. Enhanced IL-1β signaling drives hematopoietic stem cell (HSC) differentiation into the myeloid lineage and is actively involved in the development and progression of hematological malignancies, including deadly acute myeloid leukemia (AML). Inhibition of IL-1β stands out as a promising therapeutic tool to treat these diseases. In the clinic, several IL-1β-blocking drugs have been FDA-approved and are used efficiently to treat autoinflammatory and autoimmune diseases, including recombinant IL-1 receptor antagonist (IL-1RN, anakinra), soluble receptors, antibodies and IL-1 traps, among others. IL-1RN competitively binds to IL-1 receptor, blocking IL-1α and IL-1β signaling. Despite the contributing role of IL-1β to hematological diseases, little is known about the endogenous IL-1 natural repressor in healthy and malignant hematopoiesis. Here, we found that low IL-1RN is a prognostic marker in AML, associated with lower survival in patients. Low IL-1RN is frequent in AML patients, particularly in those with lower maturation/differentiation profiles as defined by the French-American-British classification (M0-M3). Boost of IL-1RN using anakinra treatment in vivo reduced the leukemic output in AML xenografts, indicating therapeutic potential. IL-1β inhibition with the human monoclonal antibody canakinumab confirmed the therapeutic potential of IL-1β blockade against AML in xenografts. Under steady-state conditions, IL-1rn represses myelopoiesis and enables B cell development given that in vivo genetic deletion of IL-1rn induced HSC differentiation into the myeloid lineage and hampered lymphoid lineage development in mice. This is mediated by IL-1β signaling via, at least in part, activation of NF-κB transcription factor activity. We further found low IL-1rn in an experimental model of pre-leukemic myelopoiesis driven by the oncogene NRAS-G12D. Loss of IL-1β repression through IL-1rn genetic deletion promoted NRAS-G12D – driven myeloproliferation, with participation of both the bone marrow hematopoietic and stromal compartments. Conversely, treatment with anakinra protected against NRAS-G12D – driven pre-leukemic myelopoiesis and improved disease progression. Taken together, our findings uncover that HSC differentiation is controlled by balanced IL-1β/IL-1rn levels under steady-state and IL-1rn represses excessive myeloproliferation and enables balanced B cell development under healthy conditions. Further, deregulation of IL-1RN leads to loss of repression of IL-1β and may underlie pre-leukemic lesion pathogenesis and AML progression. We further provide a new rationale for IL-1β blockade therapeutic potential in AML and a new means through administration of anakinra.
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Hellsten, Benjamin; Arranz, Lorena & Cuminetti, Vincent
(2021).
How does the succinate receptor interfere with
the expression of LepR, Adipoq and Nestin in the bone marrow.
UiT Norges arktiske universitet.
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Olsen, Håkon; Arranz, Lorena & Geiseler, Samuel Jakob
(2021).
Characterization of the bone marrow
microenvironment in succinate receptor knock-out mice.
UiT Norges arktiske universitet.
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Dahlquist, Gabriel Cyrus & Arranz, Lorena
(2020).
Succinate receptor 1 presence in the bone
marrow.
UiT Norges arktiske universitet.
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Ruiz-Florit, Adrián & Arranz, Lorena
(2019).
Neuropatía de la médula ósea en la leucemia mieloide aguda.
Universitat Rovira i Virgili.
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Golnarnik, Golnaz; Arranz, Lorena & Bernal, Aurora
(2019).
Neural Control in Acute Myeloid Leukemia Development: Study of the Ultrastructure of Neuroglial Components of the Bone Marrow Microenvironment in a Mouse Model of Myeloid Leukemia.
UiT Norges arktiske universitet.
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Boydens, Riet & Arranz, Lorena
(2018).
Role of TRAF6 in acute myeloid leukaemia development examined in vitro on NOMO-1 and THP-1 cell lines.
VIVES University College .
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Schmidt-Morgenroth, Ines & Arranz, Lorena
(2018).
Potential role of intermediate metabolite succinate as mediator of intercellular communication in acute myeloid leukemia.
Universite Clermont Auvergne.
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Serulla, Marc & Arranz, Lorena
(2016).
Neuroglial regulation of the stem cell niche in NRASG12D myeloid neoplasia.
Universidad de Lleida.
