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• 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.

• 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.

• 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.

• Luche, Elodie; Robert, Virginie; Cuminetti, Vincent; Pomié, Céline; Sastourné-Arrey, Quentin & Waget, Aurélie [Vis alle 13 forfattere av denne artikkelen] (2017). Corrupted adipose tissue endogenous myelopoiesis initiates diet-induced metabolic disease. eLIFE. doi: 10.7554/eLife.23194. Fulltekst i vitenarkiv
• Carrière, Audrey; Jeanson, Yannick; Côté, Julie-Anne; Dromard, Cécile; Galinier, Anne & Menzel, S [Vis alle 17 forfattere av denne artikkelen] (2017). Identification of the ectoenzyme CD38 as a marker of committed preadipocytes. International Journal of Obesity. ISSN 0307-0565. doi: 10.1038/ijo.2017.140. Fulltekst i vitenarkiv
• Cousin, Béatrice; Casteilla, Louis; Laharrague, Patrick; Luche, Elodie; Lorsignol, Anne & Cuminetti, Vincent [Vis alle 7 forfattere av denne artikkelen] (2016). Immuno-metabolism and adipose tissue: The key role of hematopoietic stem cells. Biochimie. ISSN 0300-9084. doi: 10.1016/j.biochi.2015.06.012. Fulltekst i vitenarkiv

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• Cuminetti, Vincent & Arranz, Lorena (2026). Control of acute myeloid leukemia by metabolites. 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; 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
• Cuminetti, Vincent (2025). What to do when your PhD project doesn’t progress (?). Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2025). Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia (AML) progression. 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
• 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
• Cuminetti, Vincent & Arranz, Lorena (2024). Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression. 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
• 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 (2022). C'est quoi une cellule souche? youtube.com. Fulltekst i vitenarkiv
• Cuminetti, Vincent & Arranz, Lorena (2022). Disruption of succinate receptor signaling promotes myeloproliferation and acute myeloid leukaemia. 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
• Cuminetti, Vincent; Luche, Elodie; Paupert, Jenny; Lorsignol, Anne; Casteilla, Louis & Cousin, Béatrice (2017). L’obésité une maladie médullaire, le diabète une maladie tissulaire? Fulltekst i vitenarkiv
• 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
• Cuminetti, Vincent & Béatrice, Cousin (2017). Etude de l'activité hématopoïétique du tissu adipeux chez la souris et l'homme. Université Toulouse III - Paul Sabatier. Fulltekst i vitenarkiv

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