Lorena Arranz

• Cuminetti, Vincent; Boet, Emeline; Heugel, Marcel; Konieczny, Joanna; Bernal, Aurora & Gomez, Manuel J. [Vis alle 23 forfattere av denne artikkelen] (2026). Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression. Nature Communications. 17(1). doi: 10.1038/s41467-026-68906-2. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Despite intriguing roles for the Succinate receptor (Sucnr1) in inflammation, few studies have explored its role in hematopoiesis. Here, we show that low SUCNR1 represents a marker for reduced overall and progression-free survival in acute myeloid leukemia (AML) patients. Succinic acid, which displays Sucnr1-dependent and independent effects, promotes disease in mouse models of pre-leukemic myelopoiesis, AML and AML xenografts, expressing low SUCNR1 . In vivo global or hematopoietic deletion of Sucnr1 induces expansion of hematopoietic stem and progenitor cells (HSPC) and hematopoiesis, whilst Sucnr1-tomato + HSPC display restricted engraftment potential. Mechanistically, activation of Sucnr1 counterbalances the stimulatory effect of intracellular succinate in HSPC and preserves HSPC transcriptional programs via control of S100a8/S100a9. Blocking S100a9 with tasquinimod rescues the defects of Sucnr1 knock-out mice, and combined with a potent Sucnr1 agonist shows therapeutic value in AML mice. In AML xenografts, single-cell RNA-sequencing reanalyses confirm SUCNR1 as a therapeutic vulnerability in patients. Together, Sucnr1 signaling restricts hematopoiesis at least partially through HSPC and via control of S100a8/S100a9. Its dysregulation emerges as contributor to malignancy that opens therapeutic avenues for AML patients.

• Mera, Aurora Bernal; Cuminetti, Vincent; Serulla, Marc; Florit, Adrian; Konieczny, Joanna & Golnarnik, Golnaz [Vis alle 12 forfattere av denne artikkelen] (2025). Bone marrow sympathetic neuropathy is a hallmark of hematopoietic malignancies and it involves severe ultrastructural damage. Experimental Hematology & Oncology. 14. doi: 10.1186/s40164-025-00614-x. Fulltekst i vitenarkiv Vis sammendrag

  The hematopoietic stem cell (HSC) niche in the bone marrow (BM) supports HSC function, fate and numbers [1]. Sympathetic fibres innervate the BM and are components of the hematopoietic stem and progenitor cell (HSPC) niche [2]. Neuropathy of the HSPC niche is present and essential for disease development in experimental models of JAK2V617F+ myeloproliferative neoplasms (MPN) and MLL-AF9+ acute myeloid leukemia (AML), and it is present in the BM of human MPN and AML patients [3–6]. Neuropathy contributes to mutant HSC expansion and represents an effective therapeutic target to block disease progression in JAK2V617F+ MPN mice [3]. The sympathomimetic agonist mirabegron restored nestin+ cells and reduced reticulin fibrosis in MPN patients [7]. Here, we show that neuropathy of the HSPC niche emerges in two additional experimental models of hematological disease including pre-leukemic myelopoiesis driven by NRASG12D and lymphoma/lymphoblastic leukemia driven by p53 deletion. Neuropathy involves severe ultrastructural damage in NRASG12D+ mice and AML patients as shown by electron microscopy. When further reinforced chemically, neuropathy has a profound impact on the experimental NRASG12D mouse model, promoting myeloid bias, reducing HSPC numbers and inducing changes in the stem cell microenvironment that include reduced numbers of mesenchymal stromal cells (MSC) and increased presence of morphologically abnormal blood vessels in BM. Together, BM neuropathy is a prevalent factor in hematopoietic malignancies that involves important degradation of sympathetic fibres and contributes to disease in a different manner depending on the driver mutation. This should be taken in consideration in the clinic, given that chemotherapy induces neuropathy of the HSC niche [8] and it is the most frequent first line treatment for AML, acute lymphoblastic leukemia and MPN patients.

• Villatoro, Alicia; Cuminetti, Vincent; Mera, Aurora Bernal; Torroja, Carlos; Cossío, Itziar & Benguría, Alberto [Vis alle 21 forfattere av denne artikkelen] (2023). Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation. Nature Communications. 14. doi: 10.1038/s41467-022-35700-9. Fulltekst i vitenarkiv Vis sammendrag

  Here we explored the role of interleukin-1β (IL-1β) repressor cytokine, IL-1 receptor antagonist (IL-1rn), in both healthy and abnormal hematopoiesis. Low IL-1RN is frequent in acute myeloid leukemia (AML) patients and represents a prognostic marker of reduced survival. Treatments with IL-1RN and the IL-1β monoclonal antibody canakinumab reduce the expansion of leukemic cells, including CD34+ progenitors, in AML xenografts. In vivo deletion of IL-1rn induces hematopoietic stem cell (HSC) differentiation into the myeloid lineage and hampers B cell development via transcriptional activation of myeloid differentiation pathways dependent on NFκB. Low IL-1rn is present in an experimental model of pre-leukemic myelopoiesis, and IL-1rn deletion promotes myeloproliferation, which relies on the bone marrow hematopoietic and stromal compartments. Conversely, IL-1rn protects against pre-leukemic myelopoiesis. Our data reveal that HSC differentiation is controlled by balanced IL-1β/IL-1rn levels under steady-state, and that loss of repression of IL-1β signaling may underlie pre-leukemic lesion and AML progression.

• Arranz, Lorena (2022). The Hematology of Tomorrow Is Here-Preclinical Models Are Not: Cell Therapy for Hematological Malignancies. Cancers. 14(3). doi: 10.3390/cancers14030580. Fulltekst i vitenarkiv Vis sammendrag

  The purpose of this review is to present the current knowledge on the clinical use of several forms of cell therapy in hematological malignancies and the preclinical models available for their study. In the context of allogeneic hematopoietic stem cell transplants, mesenchymal stromal cells are pursued to help stem cell engraftment and expansion, and control graft versus host disease. We further summarize the status of promising forms of cellular immunotherapy including CAR T cell and CAR NK cell therapy aimed at eradicating the cells of origin of leukemia, i.e., leukemia stem cells. Updates on other forms of cellular immunotherapy, such as NK cells, CIK cells and CAR CIK cells, show encouraging results in AML. The considerations in available in vivo models for disease modelling and treatment efficacy prediction are discussed, with a particular focus on their strengths and weaknesses for the study of healthy and diseased hematopoietic stem cell reconstitution, graft versus host disease and immunotherapy. Despite current limitations, cell therapy is a rapidly evolving field that holds the promise of improved cure rates, soon. As a result, we may be witnessing the birth of the hematology of tomorrow. To further support its development, improved preclinical models including humanized microenvironments in mice are urgently needed.

• Vilaplana-Lopera, Nuria; Cuminetti, Vincent; Almaghrabi, Ruba; Papatzikas, Grigorios; Rout, Ashok Kumar & Jeeves, Mark [Vis alle 19 forfattere av denne artikkelen] (2022). Crosstalk between AML and stromal cells triggers acetate secretion through the metabolic rewiring of stromal cells. eLIFE. 11, s. 1–29. doi: 10.7554/eLife.75908. Fulltekst i vitenarkiv Vis sammendrag

  Acute myeloid leukaemia (AML) cells interact and modulate components of their surrounding microenvironment into their own benefit. Stromal cells have been shown to support AML survival and progression through various mechanisms. Nonetheless, whether AML cells could establish beneficial metabolic interactions with stromal cells is underexplored. By using a combination of human AML cell lines and AML patient samples together with mouse stromal cells and a MLL-AF9 mouse model, here we identify a novel metabolic crosstalk between AML and stromal cells where AML cells prompt stromal cells to secrete acetate for their own consumption to feed the tricarboxylic acid cycle (TCA) and lipid biosynthesis. By performing transcriptome analysis and tracer-based metabolic NMR analysis, we observe that stromal cells present a higher rate of glycolysis when co-cultured with AML cells. We also find that acetate in stromal cells is derived from pyruvate via chemical conversion under the influence of reactive oxygen species (ROS) following ROS transfer from AML to stromal cells via gap junctions. Overall, we present a unique metabolic communication between AML and stromal cells and propose two different molecular targets, ACSS2 and gap junctions, that could potentially be exploited for adjuvant therapy.

• Toda, Irene Martínez de; Rattan, Suresh IS; Fuente, Mónica De la & Arranz, Lorena (2021). Female Mice Reaching Exceptionally High Old Age Have Preserved 20S Proteasome Activities. Antioxidants. 10(9), s. 1397–1397. doi: 10.3390/antiox10091397. Fulltekst i vitenarkiv Vis sammendrag

  Oxidized, damaged and misfolded proteins accumulate during aging and contribute to impaired cell function and tissue homeodynamics. Damaged proteins are degraded by cellular clearance mechanisms like the 20S proteasome. Aging relates to low 20S proteasome function, whereas long-lived species show high levels. However, contradictory results exist depending on the tissue or cell type and it is unknown how the 20S proteasome functions in exceptionally old mice. The aim of this study was to investigate two proteasome activities (caspase-like and chymotrypsin-like) in several tissues (lung, heart, axillary lymph nodes, liver, kidney) and cells (peritoneal leukocytes) from adult (28 ± 4 weeks, n = 12), old (76 ± 4 weeks, n = 9) and exceptionally old (128 ± 4 weeks, n = 9) BALB/c female mice. The results show different age-related changes depending on the tissue and the activity considered, so there is no universal decline in proteasome function with age in female mice. Interestingly, exceptionally old mice displayed better maintained proteasome activities, suggesting that preserved 20S proteasome is associated with successful aging

• Mate, Ianire; Toda, Irene Martínez de; Arranz, Lorena; Álvarez-Sala, Jose Luis & Fuente, Mónica De la (2021). Accelerated immunosenescence, oxidation and inflammation lead to a higher biological age in COPD patients. Experimental Gerontology. ISSN 0531-5565. 154, s. 111551–111551. doi: 10.1016/j.exger.2021.111551. Fulltekst i vitenarkiv
• Villatoro, Alicia; Konieczny, Joanna; Cuminetti, Vincent & Arranz, Lorena (2020). Leukemia Stem Cell Release From the Stem Cell Niche to Treat Acute Myeloid Leukemia. Frontiers in Cell and Developmental Biology. 8, s. 607–607. doi: 10.3389/fcell.2020.00607. Fulltekst i vitenarkiv Vis sammendrag

  Acute myeloid leukemia (AML) is a heterogeneous, complex, and deadly disease, whose treatment has hardly evolved for decades and grounds on the use of intensive chemotherapy regimens. Chemotherapy helps reduce AML bulk, but promotes relapse in the long-run by selection of chemoresistant leukemia stem cells (LSC). These may diversify and result in progression to more aggressive forms of AML. <i>In vivo</i> models suggest that the bone marrow stem cell niche helps LSC stay dormant and protected from chemotherapy. Here, we summarize relevant changes in stem cell niche homing and adhesion of AML LSC vs. healthy hematopoietic stem cells, and provide an overview of clinical trials aiming at targeting these processes for AML treatment and future directions within this field. Promising results with various non-mutation-targeted novel therapies directed to LSC eradication via interference with their anchoring to the stem cell niche have encouraged on-going or future advanced phase III clinical trials. In the coming years, we may see a shift in the focus of AML treatment to LSC-directed therapies if the prospect of improved cure rates holds true. In the future, AML treatment should lean toward personalized therapies using combinations of these compounds plus mutation-targeted agents and/or targeted delivery of chemotherapy, aiming at LSC eradication with reduced side effects.

• Cuminetti, Vincent & Arranz, Lorena (2019). Bone marrow adipocytes: The enigmatic components of the hematopoietic stem cell niche. Journal of Clinical Medicine. 8(5), s. 707–707. doi: 10.3390/jcm8050707. Fulltekst i vitenarkiv Vis sammendrag

  Bone marrow adipocytes (BMA) exert pleiotropic roles beyond mere lipid storage and filling of bone marrow (BM) empty spaces, and we are only now beginning to understand their regulatory traits and versatility. BMA arise from the differentiation of BM mesenchymal stromal cells, but they seem to be a heterogeneous population with distinct metabolisms, lipid compositions, secretory properties and functional responses, depending on their location in the BM. BMA also show remarkable differences among species and between genders, they progressively replace the hematopoietic BM throughout aging, and play roles in a range of pathological conditions such as obesity, diabetes and anorexia. They are a crucial component of the BM microenvironment that regulates hematopoiesis, through mechanisms largely unknown. Previously considered as negative regulators of hematopoietic stem cell function, recent data demonstrate their positive support for hematopoietic stem cells depending on the experimental approach. Here, we further discuss current knowledge on the role of BMA in hematological malignancies. Early hints suggest that BMA may provide a suitable metabolic niche for the malignant growth of leukemic stem cells, and protect them from chemotherapy. Future in vivo functional work and improved isolation methods will enable determining the true essence of this elusive BM hematopoietic stem cell niche component, and confirm their roles in a range of diseases. This promising field may open new pathways for efficient therapeutic strategies to restore hematopoiesis, targeting BMA.

• Mera, Aurora Bernal & Arranz, Lorena (2018). Nestin-expressing progenitor cells: function, identity and therapeutic implications. Cellular and Molecular Life Sciences (CMLS). ISSN 1420-682X. 75(12), s. 2177–2195. doi: 10.1007/s00018-018-2794-z. Fulltekst i vitenarkiv Vis sammendrag

  The neuroepithelial stem cell protein, or Nestin, is a cytoskeletal intermediate filament initially characterized in neural stem cells. However, current extensive evidence obtained in in vivo models and humans shows presence of Nestin+ cells with progenitor and/or regulatory functions in a number of additional tissues, remarkably bone marrow. This review presents the current knowledge on the role of Nestin in essential stem cell functions, including self-renewal/proliferation, differentiation and migration, in the context of the cytoskeleton. We further discuss the available in vivo models for the study of Nestin⁺ cells and their progeny, their function and elusive nature in nervous system and bone marrow, and their potential mechanistic role and promising therapeutic value in preclinical models of disease. Future improved in vivo models and detection methods will allow to determine the true essence of Nestin⁺ cells and confirm their potential application as therapeutic target in a range of diseases.

• Konieczny, Joanna & Arranz, Lorena (2018). Updates on old and weary haematopoiesis. International Journal of Molecular Sciences. ISSN 1661-6596. 19:2567(9), s. 1–14. doi: 10.3390/ijms19092567. Fulltekst i vitenarkiv Vis sammendrag

  Blood formation, or haematopoiesis, originates from haematopoietic stem cells (HSCs), whose functions and maintenance are regulated in both cell- and cell non-autonomous ways. The surroundings of HSCs in the bone marrow create a specific niche or microenvironment where HSCs nest that allows them to retain their unique characteristics and respond rapidly to external stimuli. Ageing is accompanied by reduced regenerative capacity of the organism affecting all systems, due to the progressive decline of stem cell functions. This includes blood and HSCs, which contributes to age-related haematological disorders, anaemia, and immunosenescence, among others. Furthermore, chronological ageing is characterised by myeloid and platelet HSC skewing, inflammageing, and expanded clonal haematopoiesis, which may be the result of the accumulation of preleukaemic lesions in HSCs. Intriguingly, haematological malignancies such as acute myeloid leukaemia have a high incidence among elderly patients, yet not all individuals with clonal haematopoiesis develop leukaemias. Here, we discuss recent work on these aspects, the ir potential underlying molecular mechanisms, and the first cues linking age-related changes in the HSC niche to poor HSC maintenance. Future work is needed for a better understanding of haematopoiesis during ageing. This field may open new avenues for HSC rejuvenation and therapeutic strategies in the elderly

• Grimolizzi, Franco & Arranz, Lorena (2018). Multiple faces of succinate beyond metabolism in blood. Haematologica. ISSN 0390-6078. 103(10), s. 1586–1592. doi: 10.3324/haematol.2018.196097. Fulltekst i vitenarkiv Vis sammendrag

  Succinate is an essential intermediate of the tricarboxylic acid cycle that exerts pleiotropic roles beyond metabolism in both physiological and pathological conditions. Recent evidence obtained in mouse models shows its essential role regulating blood cell function through various mechanisms that include pseudohypoxia responses by hypoxiainducible factor-1α activation, post-translational modifications like succinylation, and communication mediated by succinate receptor 1. Hence, succinate links metabolism to processes like gene expression and intercellular communication. Interestingly, succinate plays key dual roles during inflammatory responses, leading to net inflammation or anti-inflammation depending on factors like the cellular context. Here, we further discuss current suggestions of the possible contribution of succinate to blood stem cell function and blood formation. Further study will be required in the future to better understand succinate biology in blood cells. This promising field may open new avenues to modulate inflammatory responses and to preserve blood cell homeostasis in the clinical setting.

• Thiyagarajan, Dhivya; Pedersen, Hege Lynum; Seredkina, Natalya; Horvei, Kjersti Daae; Arranz, Lorena & Sonneveld, Ramon [Vis alle 9 forfattere av denne artikkelen] (2018). IL-1β Promotes a New Function of DNase I as a Transcription Factor for the Fas Receptor Gene. Frontiers in Cell and Developmental Biology. 6. doi: 10.3389/fcell.2018.00007. Fulltekst i vitenarkiv Vis sammendrag

  Recently we described that endonuclease inactive DNase I translocated into the nucleus in response to increased endogenous IL-1β expression. Here, we demonstrate impact and function of translocated DNase I in tubular cells. Effect of cytokines on expression level and nuclear localisation of DNase I and corresponding levels of Fas receptor (FasR) and IL-1β were determined by confocal microscopy, qPCR and western blot analyses, in presence or absence of siRNA against IL-1β and DNase I mRNA. Nuclear DNase I bound to the FAS promotor region as determined by chromatin immuno-precipitation analysis. Data demonstrate that; (i) translocation of DNase I depended on endogenous de novo-expressed IL-1β, (ii) nuclear DNase I bound FAS DNA, (iii) FasR expression increased after translocation of DNase I, (iv) interaction of exogenous Fas ligand (FasL) with upregulated FasR induced apoptosis in human tubular cells stimulated with TNFα. Thus, translocated DNase I most probably binds the promoter region of the FAS gene and function as a transcription factor for FasR. In conclusion, DNase I not only executes chromatin degradation during apoptosis and necrosis, but also primes the cells for apoptosis by enhancing FasR expression.

• Arranz, Lorena; Sanchez, Maria Del Mar Arriero & Villatoro, Alicia (2017). Interleukin-1β as emerging therapeutic target in hematological malignancies and potentially in their complications. Blood reviews. ISSN 0268-960X. 31(5), s. 306–317. doi: 10.1016/j.blre.2017.05.001. Fulltekst i vitenarkiv Vis sammendrag

  Interleukin-1β (IL-1β) is a pleiotropic cytokine that exerts multiple roles in both physiological and pathological conditions. It is produced by different cell subsets, and drives a wide range of inflammatory responses in numerous target cells. Enhanced IL-1β signaling is a common event in patients of hematological malignancies. Recent body of evidence obtained in preclinical models shows the pathogenic role of these alterations, and the promising therapeutic value of IL-1 targeting. In this review, we further highlight a potential contribution of IL-1β linking to complications and autoimmune disease that should be investigated in future studies. Hence, drugs that target IL-1 may be helpful to improve outcome or reduce morbidity in patients. Some of them are FDA-approved, and used efficiently against autoimmune diseases, like IL-1 receptor antagonist. In the clinic, however, this agent seems to have limited properties. Current improved drugs will allow to determine the true potential of IL-1 and IL-1β targeting as therapy in hematological malignancies and their related complications.

Se alle arbeider i NVA

• Cuminetti, Vincent & Arranz, Lorena (2026). Control of acute myeloid leukemia by metabolites. Fulltekst i vitenarkiv
• Heugel, Marcel & Arranz, Lorena (2026). Exploring the transformation potential of hematopoietic stem cells with defects in IL1RN, and their therapeutic targeting. Fulltekst i vitenarkiv
• Arranz, Lorena (2026). Therapeutic targeting of stem cells and their niches in myeloid malignancies. Fulltekst i vitenarkiv
• Heugel, Marcel & Arranz, Lorena (2026). Exploring the transformation potential of human hematopoietic stem cells with defects in IL1RN, and their therapeutic targeting. Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2026). Control of hematopoiesis by Succinate receptor 1 in the stem cell niche. Fulltekst i vitenarkiv
• Arranz, Lorena (2026). Knowledge in use: NOK 4,9 million to innovative UiO researchers. [Internet]. /https://www.uio.no/ . doi: https:/www.uio.no/english/about/news-and-events/news/2026/uio-innovation-funds-2026.html. Fulltekst i vitenarkiv
• Arranz, Lorena (2026). ISEH 5th Annual Virtual Career Fair. Fulltekst i vitenarkiv Vis sammendrag

  New Investigators Committee Presents: ISEH 5th Annual Virtual Career Fair Thank you for a successful Career Fair! Are you searching for a new position in the field of hematology? Or are you seeking to recruit talented scientists for your research groups? Join us for the New Investigator Committee virtual career fair! The New Investigator Committee of the International Society for Experimental Hematology (ISEH) is excited to announce our fifth annual FREE virtual career fair. This unique event aims to connect trainees with hiring faculty from around the world. Using a "speed networking" format, hiring faculty will have the chance to engage in one-on-one conversations with individuals currently in the job market. Our goal is to assist trainees in finding valuable training opportunities in hematology labs, while also helping faculty identify talented scientists to join their teams.

• Arranz, Lorena; Carlsten, Mattias & Newman, Rhiannon (2026). Life After YERM: How the Young EHA Research Meeting Shaped Careers. doi: https:/open.spotify.com/episode/0VtPZopANNt1RDlMH3ZaXI. Fulltekst i vitenarkiv
• Arranz, Lorena; Carlsten, Mattias & Newman, Rhiannon (2026). Life After YERM: How the Young EHA Research Meeting Shaped Careers. doi: https:/www.youtube.com/watch?v=VD8eLSrDR1w. Fulltekst i vitenarkiv
• Arranz, Lorena; Cuminetti, Vincent & Doeland, Elin Martine (2026). Vil bekjempe leukemi ved å stoppe stamceller fra å bli til kreftceller. [Internet]. https://www.uio.no/. doi: https:/www.uio.no/forskning/forskningsnytt/artikler/2026/vil-bekjempe-leukemi-stoppe-stamceller-fra-bli-til-kreftceller.html. Fulltekst i vitenarkiv
• Arranz, Lorena; Cuminetti, Vincent & Doeland, Elin Martine (2026). Aim to combat leukaemia by stopping stem cells from becoming cancer cells. [Internet]. /https://www.uio.no/ . doi: https:/www.uio.no/english/research/research-news/articles/2026/aim-to-combat-leukaemia-by-stopping-stem-cells-cancer-cells.html. Fulltekst i vitenarkiv
• Arranz, Lorena & Øksne, Rannveig (2026). 9 millioner til forskning på målrettede blodkreftbehandlinger. [Internet]. https://www.blodkreftforeningen.no/. doi: https:/www.blodkreftforeningen.no/om-oss/nyhetsarkiv/tildeling-neurotarget. Fulltekst i vitenarkiv
• Henriquez, Daniela Cabrera & Arranz, Lorena (2026). Mapping succinate receptor 1 expression and function in the bone marrow niche. Fulltekst i vitenarkiv
• Arranz, Lorena (2026). Neuropathy of the stem cell niche in myeloid leukemias – potential for therapeutic targeting. Fulltekst i vitenarkiv
• Arranz, Lorena (2026). Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression. Fulltekst i vitenarkiv
• Arranz, Lorena (2026). Therapeutic targeting of stem cells and their niches in myeloid malignancies. Fulltekst i vitenarkiv Vis sammendrag

  Our research group “Stem Cells, Ageing and Cancer” aims at providing insights into mechanisms of hematopoietic stem cell malignant transformation, including interactions of this cell with its surrounding microenvironment, and a focus on inflammation, signaling oncometabolites and various cellular components of the stem cell niche. Our goal is the identification of novel therapeutic targets of potential clinical interest for myeloid malignancies. We will give an overview of our research and present unpublished observations accepted in principle in Nature Communications, where we have uncovered an important role for the metabolite succinate and its membrane receptor Succinate receptor (Sucnr1) in the regulation of hematopoiesis in health and malignancy. Our work suggests that Sucnr1 signaling restricts hematopoiesis at least partially via the hematopoietic stem and progenitor cell compartment and control of S100a9. The dysregulation of Sucnr1 emerges as contributor to malignancy, accounting for SUCNR1 expression as a predictor of prognosis in acute myeloid leukemia (AML) patients and opening new potential therapeutic avenues for these patients.

• Arranz, Lorena (2026). Potential for therapeutic targeting of stem cells and their niches in myeloid malignancies. Fulltekst i vitenarkiv Vis sammendrag

  Lorena Arranz's research group “Stem Cells, Ageing and Cancer” aims at providing insights into mechanisms of hematopoietic stem cell malignant transformation, including interactions of this cell with its surrounding microenvironment, and a focus on inflammation, signaling oncometabolites and various cellular components of the stem cell niche. Their goal is the identification of novel therapeutic targets of potential clinical interest for myeloid malignancies. Dr Arranz will give an overview of her research and present their group's recent work, where they have uncovered an important role for the metabolite succinate and its membrane receptor Succinate receptor (Sucnr1) in the regulation of hematopoiesis in health and malignancy. Their work suggests that Sucnr1 signaling restricts hematopoiesis at least partially via the hematopoietic stem and progenitor cell compartment and control of S100a9. The dysregulation of Sucnr1 emerges as contributor to malignancy, accounting for SUCNR1 expression as a predictor of prognosis in acute myeloid leukemia (AML) patients and opening new potential therapeutic avenues for these patients.

• Arranz, Lorena (2025). Neuropathy of the stem cell niche in myeloid leukemias – potential for therapeutic targeting. Fulltekst i vitenarkiv
• Arranz, Lorena (2025). Uncovering novel treatments for patients of myeloid leukemias. Fulltekst i vitenarkiv
• Arranz, Lorena (2025). Uncovering novel treatments for patients of myeloid leukemias. Fulltekst i vitenarkiv
• Heugel, Marcel & Arranz, Lorena (2025). Exploring the transformation potential of haematopoietic stem cells with defects in IL1RN, and their therapeutic targeting. Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2025). Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia (AML) progression. Fulltekst i vitenarkiv
• Fuertes, Alba Soto & Arranz, Lorena (2025). Development of a method to predict patients of myeloid malignancies with best chances of success for blocking inflammation as therapeutic strategy. Fulltekst i vitenarkiv
• Arranz, Lorena & Lawrence, Leah (2025). Which Studies at EHA 2025 May Change Practice? [Internet]. Oncology News Central. Fulltekst i vitenarkiv Vis sammendrag

  The European Hematology Association 2025 Congress kicks off on June 12 in Milan, Italy, and will provide updates “on the most recent breakthroughs in both clinical and translational hematology,” says Lorena Arranz, PhD, a member of the meeting’s Scientific Program Committee.

• Arranz, Lorena (2025). Therapeutic targeting of stem cells and their niches in age-related myeloid malignancies. Fulltekst i vitenarkiv
• Arranz, Lorena (2025). Restoring the control over inflammation as therapy against acute myeloid leukemia. Fulltekst i vitenarkiv
• Arranz, Lorena (2025). Therapeutic targeting of stem cells and their niches in myeloid malignancies. Fulltekst i vitenarkiv
• Cuminetti, Vincent; Konieczny, Joanna; Mera, Aurora Bernal; Oliver, Marc Ferre; Gomez, Manuel José & Vilaplana-Lopera, Nuria [Vis alle 18 forfattere av denne artikkelen] (2024). Succinate receptor 1 signaling regulates hematopoiesis via S100/a8 and S100/a9 in health and malignancy. Fulltekst i vitenarkiv
• Arranz, Lorena (2024). Introduction to Bone Marrow Physiology and Pathophysiology - Opportunities for Imaging. Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2024). Succinate receptor 1 signaling regulates hematopoiesis via S100/a8 and S100/a9 in health and malignancy. Fulltekst i vitenarkiv
• Cuminetti, Vincent; Konieczny, Joanna; Boet, Emeline; Mera, Aurora Bernal; Oliver, Marc Ferré & Gomez, Manuel José [Vis alle 20 forfattere av denne artikkelen] (2024). Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression. Fulltekst i vitenarkiv
• Arranz, Lorena (2024). Restoring the control over inflammation as therapy against myeloid malignancies. Fulltekst i vitenarkiv
• Arranz, Lorena (2024). Therapeutic targeting of stem cells and their niches in disease: A focus on myeloid malignancies. Fulltekst i vitenarkiv
• Arranz, Lorena (2024). Restoring the control over inflammation as therapy against myeloid malignancies. Fulltekst i vitenarkiv
• Arranz, Lorena & Juul, Kjersti (2024). Et spirende forskningssenter. [Journal]. www.blodkreftforeningen.no. Fulltekst i vitenarkiv
• Arranz, Lorena (2024). Regulatory mechanisms of hematopoietic stem and progenitor cell function in health and malignancy. Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2024). Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression. Fulltekst i vitenarkiv
• Heugel, Marcel & Arranz, Lorena (2024). Exploring the transformation potential of haematopoietic stem cells with defects in IL1-RN. Fulltekst i vitenarkiv
• Arranz, Lorena & Stranden, Anne Lise (2023). Norwegian discovery gives hope for blood cancer patients. [Internet]. https://www.sciencenorway.no/. Fulltekst i vitenarkiv
• Arranz, Lorena & Stranden, Anne Lise (2023). Norsk funn gir håp for blodkreft­pasienter. [Internet]. https://www.forskning.no/. Fulltekst i vitenarkiv
• Arranz, Lorena & Bludd, Ellen Kathrine (2023). Leukemipasienter kan få hjelp av ny metode. [Internet]. https://uit.no/nyheter/artikkel?p_document_id=800155. Fulltekst i vitenarkiv
• 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/. Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2023). Succinate receptor 1 signaling regulates hematopoiesis in health and malignancy. Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2023). Succinate receptor 1 signaling regulates hematopoiesis in health and malignancy. Fulltekst i vitenarkiv
• Gonzalez, Alicia Elena Villatoro; Cuminetti, Vincent; Mera, Aurora Bernal; Torroja, Carlos; Cossío, Itziar & Benguría, Alberto [Vis alle 22 forfattere av denne artikkelen] (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. 14(1). doi: 10.1038/s41467-023-39601-3. Fulltekst i vitenarkiv
• Arranz, Lorena (2023). Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation. Fulltekst i vitenarkiv Vis sammendrag

  In this talk, Dr Arranz will discuss their recent findings showing how defective resolution of interleukin-1B-driven inflammation may underlie pre-leukemic lesion and acute myeloid leukemia progression. This work was recently published in Nature Communications.

• Arranz, Lorena & Juul, Kjersti (2023). Nytt håp for voksne leukemipasienter. [Journal]. I margen nr. 1, 2023, 23. Fulltekst i vitenarkiv Vis sammendrag

  Norske forskere er i ferd med å utvikle en behandling som øker overlevelsen for voksne leukemipasienter.

• Ferré, Marc & Arranz, Lorena (2023). Exploring the transformation potential of haematopoietic stem cells under germinal NTRK1 mutations. Fulltekst i vitenarkiv
• Arranz, Lorena & Marin, Diego (2022). Buscar cura para las leucemias más agresivas es nuestra aventura diaria. [Journal]. https://www.larioja.com/. Fulltekst i vitenarkiv
• Cuminetti, Vincent; Konieczny, Joanna; Bernal, Aurora; Villatoro, Alicia; Taman, Hagar & Ristic, Marko [Vis alle 12 forfattere av denne artikkelen] (2022). Disruption of succinate receptor signaling promotes myeloproliferation and acute myeloid leukaemia. HemaSphere. 6, s. 307–308. doi: 10.1097/01.HS9.0000843896.71224.8d. Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2022). Disruption of succinate receptor signaling promotes myeloproliferation and acute myeloid leukaemia. Fulltekst i vitenarkiv
• Arranz, Lorena (2022). Pathophysiology of stem cells. Fulltekst i vitenarkiv
• Arranz, Lorena (2022). Therapeutic targeting of stem cells and their niches in myeloid malignancies. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Arranz, Lorena (2022). Targeting stem cells and their niches in myeloid malignancies. Fulltekst i vitenarkiv
• Arranz, Lorena (2021). Therapeutic targeting of stem cells and their niches in disease: A focus on myeloid malignancies. Fulltekst i vitenarkiv
• Arranz, Lorena (2021). Targeting stem cells and their niches in myeloid malignancies. Fulltekst i vitenarkiv
• Arranz, Lorena (2021). Endogenous IL-1 receptor antagonist represses myelopoiesis and guards against leukemia. Fulltekst i vitenarkiv
• Arranz, Lorena (2021). Targeting the stem cell niche in myeloid malignancies. Fulltekst i vitenarkiv
• Arranz, Lorena (2021). Cancer Stem Cells in Hematological Cancers. Fulltekst i vitenarkiv
• Arranz, Lorena (2021). Stem cells and their niche as a basis for future therapies. Fulltekst i vitenarkiv
• Arranz, Lorena & Armas, Antonio (2020). Celulas madre en las neoplasias hematopoyeticas. [Radio]. https://www.investigadoresporelmundo.com/podcast/. Fulltekst i vitenarkiv
• Arranz, Lorena (2020). Targeting the stem cell niche in myeloid malignancies. Fulltekst i vitenarkiv
• Arranz, Lorena (2020). Stem cells and their niche as a basis for future therapies. Fulltekst i vitenarkiv
• Cuenca-Zamora, EJ; Ruiz-Pividal, JF; Zamora-Plana, L; Bellosino, B; Morena-Barrio, ME De la & Bohdan, N [Vis alle 15 forfattere av denne artikkelen] (2019). THE GERMINAL VARIANTS RS6336/RS6339 OF NTRK1 PREDISPOSE TO CHRONIC MYELOPROLIFERATIVE NEOPLASIAS. Haematologica. ISSN 0390-6078. 104, s. 59–60. Fulltekst i vitenarkiv
• Arranz, Lorena (2019). IL-1 receptor antagonist prevents IL-1β-induced myeloid bias in hematopoietic stem cells and protects from leukemia. Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2019). Investigating the role of succinate receptor 1 as regulator of steady-state and malignant hematopoeisis. Fulltekst i vitenarkiv
• Arranz, Lorena (2019). Imbalance of IL-1β signaling over IL-1 receptor antagonist favors myeloid output and promotes malignancy in leukemia. Fulltekst i vitenarkiv
• Bernal, Aurora & Arranz, Lorena (2019). Bone marrow neuropathy in acute myeloid leukemia. Fulltekst i vitenarkiv
• Arranz, Lorena (2018). Novel Regulatory Network of Haematopoiesis in Acute Myeloid Leukaemia. Fulltekst i vitenarkiv
• Arranz, Lorena (2018). El nicho medular y la inflamacion en las NMP. Fulltekst i vitenarkiv
• Arranz, Lorena (2018). Novel regulatory networks of hematopoiesis in health and disease. Fulltekst i vitenarkiv
• Ho, Ya-Hsuan; Toro, Raquel del; Rivera-Torres, Jose; Rak, Justyna; Korn, Claudia & García-García, Andrés [Vis alle 23 forfattere av denne artikkelen] (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, s. 3842–3842. Fulltekst i vitenarkiv
• Bernal, Aurora; Konieczny, Joanna; Villatoro, Alicia & Arranz, Lorena (2018). DOES AGING FOSTER TRANSFORMATION TO ACUTE MYELOID LEUKAEMIA? Fulltekst i vitenarkiv
• Arranz, Lorena (2018). Stem Cells, Aging and Cancer @ UiT. Fulltekst i vitenarkiv
• Villatoro, Alicia & Arranz, Lorena (2018). Anti-inflammatory properties of the bone marrow in leukemic transformation. Fulltekst i vitenarkiv
• Bernal, Aurora; Serulla, Marc; Villatoro, Alicia; Gargiulo, Ernesto & Arranz, Lorena (2017). Neuroglial Regulation of the Hematopoietic Stem Cell Niche in Acute Myeloid Leukemia. Fulltekst i vitenarkiv
• Arranz, Lorena (2017). Role for the Stem Cell Niche in Myeloid Neoplasias. Fulltekst i vitenarkiv
• Arranz, Lorena (2017). Role for the Stem Cell Niche in Myeloid Neoplasias. Fulltekst i vitenarkiv
• Villatoro, Alicia & Arranz, Lorena (2022). The role of interleukin-1 receptor antagonist in normal and malignant hematopoiesis. UiT Norges arktiske universitet. Fulltekst i vitenarkiv Vis sammendrag

  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.

• 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. Fulltekst i vitenarkiv
• Olsen, Håkon; Arranz, Lorena & Geiseler, Samuel Jakob (2021). Characterization of the bone marrow microenvironment in succinate receptor knock-out mice. UiT Norges arktiske universitet. Fulltekst i vitenarkiv
• Dahlquist, Gabriel Cyrus & Arranz, Lorena (2020). Succinate receptor 1 presence in the bone marrow. UiT Norges arktiske universitet. Fulltekst i vitenarkiv
• Ruiz-Florit, Adrián & Arranz, Lorena (2019). Neuropatía de la médula ósea en la leucemia mieloide aguda. Universitat Rovira i Virgili. Fulltekst i vitenarkiv
• Konieczny, Joanna; Arranz, Lorena & Bernal, Aurora (2018). Does ageing foster transformation to acute myeloid leukaemia? UiT Norges arktiske universitet. Fulltekst i vitenarkiv
• 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 . Fulltekst i vitenarkiv
• Schmidt-Morgenroth, Ines & Arranz, Lorena (2018). Potential role of intermediate metabolite succinate as mediator of intercellular communication in acute myeloid leukemia. Universite Clermont Auvergne. Fulltekst i vitenarkiv

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