{"entity": "researcher", "timestamp": "2026-08-17T17:19:49.845Z", "family": "Puente-Moncada", "given": "Noelia", "initials": "N", "orcid": "0000-0002-5996-2349", "affiliations": ["LUND UNIVERSITY, Lund, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/1d4ac0bd551b4463a22e3f60470c2b6d.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/1d4ac0bd551b4463a22e3f60470c2b6d"}}, "publications": [{"entity": "publication", "iuid": "fce0b1c5ed3042108958987c9ce95838", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fce0b1c5ed3042108958987c9ce95838.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fce0b1c5ed3042108958987c9ce95838"}}, "title": "Single-cell genomics details the maturation block in BCP-ALL and identifies therapeutic vulnerabilities in DUX4-r cases.", "authors": [{"family": "Thorsson", "given": "Hanna", "initials": "H", "orcid": "0000-0001-5393-2942", "researcher": {"href": "https://publications.scilifelab.se/researcher/7667559679a64a999d508ff7fa506782.json"}}, {"family": "Henningsson", "given": "Rasmus", "initials": "R"}, {"family": "Puente-Moncada", "given": "Noelia", "initials": "N", "orcid": "0000-0002-5996-2349", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4ac0bd551b4463a22e3f60470c2b6d.json"}}, {"family": "Pe\u00f1a-Mart\u00ednez", "given": "Pablo", "initials": "P", "orcid": "0000-0002-0789-6431", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d675e892dfc4334bb12051e004a7711.json"}}, {"family": "Sj\u00f6str\u00f6m", "given": "Ludvig", "initials": "L", "orcid": "0009-0004-3140-1998", "researcher": {"href": "https://publications.scilifelab.se/researcher/8421a85c20544aa286a55f502c52fb1d.json"}}, {"family": "\u00c5gerstam", "given": "Helena", "initials": "H"}, {"family": "Sand\u00e9n", "given": "Carl", "initials": "C", "orcid": "0000-0002-8931-9565", "researcher": {"href": "https://publications.scilifelab.se/researcher/29207805704e4660b20eebc87efe5282.json"}}, {"family": "Rissler", "given": "Marianne", "initials": "M"}, {"family": "Castor", "given": "Anders", "initials": "A", "orcid": "0009-0007-4634-0704", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed2d2dab933049f5b69cdf0ff1e1d8a1.json"}}, {"family": "Marquart", "given": "Hanne", "initials": "H", "orcid": "0000-0001-9740-6522", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9476b7116154ea9990d7c61c675c794.json"}}, {"family": "Modvig", "given": "Signe", "initials": "S", "orcid": "0000-0001-9113-1097", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb23402f5100434ea091e47564c61654.json"}}, {"family": "Paulsson", "given": "Kajsa", "initials": "K", "orcid": "0000-0001-7950-222X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2033b23811f1432c90ad860dd993e7a8.json"}}, {"family": "Pronk", "given": "Cornelis Jan", "initials": "CJ", "orcid": "0000-0002-0073-9660", "researcher": {"href": "https://publications.scilifelab.se/researcher/76e42ba48d824aa0b42e871e9f11b00a.json"}}, {"family": "Schmiegelow", "given": "Kjeld", "initials": "K", "orcid": "0000-0002-0829-4993", "researcher": {"href": "https://publications.scilifelab.se/researcher/67205019fcc548d3a34ef667de551fde.json"}}, {"family": "Hyrenius-Wittsten", "given": "Axel", "initials": "A", "orcid": "0000-0002-1239-4954", "researcher": {"href": "https://publications.scilifelab.se/researcher/26ee89834c8f409a9445c5b16d8f691e.json"}}, {"family": "Orsmark-Pietras", "given": "Christina", "initials": "C"}, {"family": "Lilljebj\u00f6rn", "given": "Henrik", "initials": "H", "orcid": "0000-0001-8703-1173", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3a75300e8c346858ce8dd8f64ecae85.json"}}, {"family": "Fioretos", "given": "Thoas", "initials": "T", "orcid": "0000-0002-3235-6154", "researcher": {"href": "https://publications.scilifelab.se/researcher/35a5c1b6023345c6b1317c590bf80680.json"}}], "type": "journal article", "published": "2024-09-26", "journal": {"issn": "1528-0020", "volume": "144", "issue": "13", "pages": "1399-1411", "title": "Blood", "issn-l": "0006-4971"}, "abstract": "B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) is the most common childhood malignancy and is driven by multiple genetic alterations that cause maturation arrest and accumulation of abnormal progenitor B cells. Current treatment protocols with chemotherapy have led to favorable outcomes but are associated with significant toxicity and risk of side effects, highlighting the necessity for highly effective, less toxic, targeted drugs, even in subtypes with a favorable outcome. Here, we used multimodal single-cell sequencing to delineate the transcriptional, epigenetic, and immunophenotypic characteristics of 23 childhood BCP-ALLs belonging to the BCR::ABL1+, ETV6::RUNX1+, high hyperdiploid, and recently discovered DUX4-rearranged (DUX4-r) subtypes. Projection of the ALL cells along the normal hematopoietic differentiation axis revealed a diversity in the maturation pattern between the different BCP-ALL subtypes. Although the BCR::ABL1+, ETV6::RUNX1+, and high hyperdiploidy cells mainly showed similarities to normal pro-B cells, DUX4-r ALL cells also displayed transcriptional signatures resembling mature B cells. Focusing on the DUX4-r subtype, we found that the blast population displayed not only multilineage priming toward nonhematopoietic cells, myeloid, and T-cell lineages, but also an activation of phosphatidylinositol 3-kinase (PI3K)/AKT signaling that sensitized the cells to PI3K inhibition in vivo. Given the multilineage priming of DUX4-r blasts with aberrant expression of myeloid marker CD371 (CLL-1), we generated chimeric antigen receptor T cells, which effectively eliminated DUX4-r ALL cells in vivo. These results provide a detailed characterization of BCP-ALL at the single-cell level and reveal therapeutic vulnerabilities in the DUX4-r subtype, with implications for the understanding of ALL biology and new therapeutic strategies.", "doi": "10.1182/blood.2023021705", "pmid": "38968149", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11451301"}, {"db": "pii", "key": "516853"}], "notes": [], "created": "2024-11-14T09:30:57.659Z", "modified": "2024-11-14T09:33:54.985Z"}, {"entity": "publication", "iuid": "cd65cb61a4fb4e6f89ead24f6c0d243c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cd65cb61a4fb4e6f89ead24f6c0d243c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cd65cb61a4fb4e6f89ead24f6c0d243c"}}, "title": "Combined GLUT1 and OXPHOS inhibition eliminates acute myeloid leukemia cells by restraining their metabolic plasticity.", "authors": [{"family": "Rodriguez-Zabala", "given": "Maria", "initials": "M"}, {"family": "Ramakrishnan", "given": "Ramprasad", "initials": "R"}, {"family": "Reinbach", "given": "Katrin", "initials": "K"}, {"family": "Ghosh", "given": "Somadri", "initials": "S"}, {"family": "Oburoglu", "given": "Leal", "initials": "L", "orcid": "0000-0003-0130-6602", "researcher": {"href": "https://publications.scilifelab.se/researcher/cac8186ea00246e6a07f421e492041e6.json"}}, {"family": "Falqu\u00e9s-Costa", "given": "Antoni", "initials": "A", "orcid": "0000-0002-5341-4472", "researcher": {"href": "https://publications.scilifelab.se/researcher/a75e19f3905e45059507c43f4722da39.json"}}, {"family": "Bellamkonda", "given": "Kishan", "initials": "K"}, {"family": "Ehinger", "given": "Mats", "initials": "M"}, {"family": "Pe\u00f1a-Mart\u00ednez", "given": "Pablo", "initials": "P", "orcid": "0000-0002-0789-6431", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d675e892dfc4334bb12051e004a7711.json"}}, {"family": "Puente-Moncada", "given": "Noelia", "initials": "N", "orcid": "0000-0002-5996-2349", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4ac0bd551b4463a22e3f60470c2b6d.json"}}, {"family": "Lilljebj\u00f6rn", "given": "Henrik", "initials": "H"}, {"family": "Cammenga", "given": "J\u00f6rg", "initials": "J"}, {"family": "Pronk", "given": "Cornelis Jan", "initials": "CJ", "orcid": "0000-0002-0073-9660", "researcher": {"href": "https://publications.scilifelab.se/researcher/76e42ba48d824aa0b42e871e9f11b00a.json"}}, {"family": "Lazarevic", "given": "Vladimir", "initials": "V"}, {"family": "Fioretos", "given": "Thoas", "initials": "T"}, {"family": "Hagstr\u00f6m-Andersson", "given": "Anna K", "initials": "AK", "orcid": "0000-0002-2904-1311", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc93a87c663d471ba64fc3be63212a89.json"}}, {"family": "Woods", "given": "Niels-Bjarne", "initials": "NB", "orcid": "0000-0001-6052-922X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c539424e21f41d1b006196a3b4b48bf.json"}}, {"family": "J\u00e4r\u00e5s", "given": "Marcus", "initials": "M", "orcid": "0000-0003-4080-7055", "researcher": {"href": "https://publications.scilifelab.se/researcher/65cacd8558004a8689985676a798ae90.json"}}], "type": "journal article", "published": "2023-09-26", "journal": {"title": "Blood Adv", "issn": "2473-9537", "volume": "7", "issue": "18", "pages": "5382-5395", "issn-l": "2473-9529"}, "abstract": "Acute myeloid leukemia (AML) is initiated and propagated by leukemia stem cells (LSCs), a self-renewing population of leukemia cells responsible for therapy resistance. Hence, there is an urgent need to identify new therapeutic opportunities targeting LSCs. Here, we performed an in vivo CRISPR knockout screen to identify potential therapeutic targets by interrogating cell surface dependencies of LSCs. The facilitated glucose transporter type 1 (GLUT1) emerged as a critical in vivo metabolic dependency for LSCs in a murine MLL::AF9-driven model of AML. GLUT1 disruption by genetic ablation or pharmacological inhibition led to suppression of leukemia progression and improved survival of mice that received transplantation with LSCs. Metabolic profiling revealed that Glut1 inhibition suppressed glycolysis, decreased levels of tricarboxylic acid cycle intermediates and increased the levels of amino acids. This metabolic reprogramming was accompanied by an increase in autophagic activity and apoptosis. Moreover, Glut1 disruption caused transcriptional, morphological, and immunophenotypic changes, consistent with differentiation of AML cells. Notably, dual inhibition of GLUT1 and oxidative phosphorylation (OXPHOS) exhibited synergistic antileukemic effects in the majority of tested primary AML patient samples through restraining of their metabolic plasticity. In particular, RUNX1-mutated primary leukemia cells displayed striking sensitivity to the combination treatment compared with normal CD34+ bone marrow and cord blood cells. Collectively, our study reveals a GLUT1 dependency of murine LSCs in the bone marrow microenvironment and demonstrates that dual inhibition of GLUT1 and OXPHOS is a promising therapeutic approach for AML.", "doi": "10.1182/bloodadvances.2023009967", "pmid": "37505194", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service", "Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10509671"}, {"db": "pii", "key": "497184"}], "notes": [], "created": "2023-08-30T07:04:12.928Z", "modified": "2025-10-17T13:03:13.479Z"}, {"entity": "publication", "iuid": "c91e733931184d15a4991de3419a6d4d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c91e733931184d15a4991de3419a6d4d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c91e733931184d15a4991de3419a6d4d"}}, "title": "The complement receptor C3AR constitutes a novel therapeutic target in NPM1-mutated AML.", "authors": [{"family": "von Palffy", "given": "Sofia", "initials": "S", "orcid": "0000-0001-5640-4037", "researcher": {"href": "https://publications.scilifelab.se/researcher/594eb39f228241efb0f055799f5eaa88.json"}}, {"family": "Thorsson", "given": "Hanna", "initials": "H"}, {"family": "Pe\u00f1a-Mart\u00ednez", "given": "Pablo", "initials": "P", "orcid": "0000-0002-0789-6431", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d675e892dfc4334bb12051e004a7711.json"}}, {"family": "Puente-Moncada", "given": "Noelia", "initials": "N", "orcid": "0000-0002-5996-2349", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4ac0bd551b4463a22e3f60470c2b6d.json"}}, {"family": "Sand\u00e9n", "given": "Carl", "initials": "C", "orcid": "0000-0002-8931-9565", "researcher": {"href": "https://publications.scilifelab.se/researcher/29207805704e4660b20eebc87efe5282.json"}}, {"family": "Blom", "given": "Anna M", "initials": "AM", "orcid": "0000-0002-1348-1734", "researcher": {"href": "https://publications.scilifelab.se/researcher/c18466d1f5614ecbb63c5d4136a02466.json"}}, {"family": "Henningsson", "given": "Rasmus", "initials": "R"}, {"family": "Juliusson", "given": "Gunnar", "initials": "G"}, {"family": "King", "given": "Ben", "initials": "B", "orcid": "0000-0001-6776-8741", "researcher": {"href": "https://publications.scilifelab.se/researcher/108b9f873836471697d74d10dd9f8707.json"}}, {"family": "Landberg", "given": "Niklas", "initials": "N", "orcid": "0000-0001-6752-6507", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ad422be3ea44e419662d514ca40cbbe.json"}}, {"family": "Lazarevic", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-1782-4423", "researcher": {"href": "https://publications.scilifelab.se/researcher/7113f0d0569247d4ac94b73ddc6ca74e.json"}}, {"family": "Orsmark-Pietras", "given": "Christina", "initials": "C"}, {"family": "Rissler", "given": "Marianne", "initials": "M"}, {"family": "Rissler", "given": "Vendela", "initials": "V"}, {"family": "\u00c5gerstam", "given": "Helena", "initials": "H"}, {"family": "J\u00e4r\u00e5s", "given": "Marcus", "initials": "M"}, {"family": "Lilljebj\u00f6rn", "given": "Henrik", "initials": "H"}, {"family": "Fioretos", "given": "Thoas", "initials": "T"}], "type": "journal article", "published": "2023-04-11", "journal": {"title": "Blood Adv", "issn": "2473-9537", "volume": "7", "issue": "7", "pages": "1204-1218", "issn-l": "2473-9529"}, "abstract": "Mutated nucleophosmin 1 (NPM1) is the most common genetic alteration in acute myeloid leukemia (AML), found in \u223c30% of cases. Although mutations in this gene are considered favorable according to current risk stratification guidelines, a large fraction of patients will experience relapse, demonstrating the urgent need for new treatment options. Therefore, we aimed to identify cell surface proteins specifically expressed on NPM1-mutated AML cells, allowing for potential targeting with antibody-based therapies. Herein, we report on an arrayed flow cytometry-based screen directed to 362 cell surface markers. In comparing the cell surface expression on NPM1-mutated AML cells with primitive (CD34+ CD38-) normal bone marrow cells, we identified the complement receptor C3AR as being specifically expressed in NPM1-mutated AML. By flow cytometry and single-cell RNA sequencing, we further show that normal hematopoietic stem and progenitor cells lack detectable C3AR gene and protein expression, making it particularly suitable as a target for antibody therapy. We also demonstrate that C3AR in combination with GPR56 distinguishes the leukemic stem cells (LSCs) in NPM1-mutated AML from the normal hematopoietic stem cells, defining the LSC population, as shown by transplantation into immunodeficient mice. Mechanistically, the stimulation of C3AR-expressing cells with C3a, the ligand of C3AR, leads to the activation of ERK1/2 and increased survival of AML cells, suggesting that this is an important signaling axis in this subtype of AML. Finally, we show that antibodies directed against C3AR efficiently elicit natural killer cell-mediated killing of primary AML cells ex vivo, highlighting C3AR as a candidate therapeutic target in NPM1-mutated AML.", "doi": "10.1182/bloodadvances.2022007682", "pmid": "36383712", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10111354"}, {"db": "pii", "key": "493242"}], "notes": [], "created": "2023-02-20T13:51:41.288Z", "modified": "2024-01-07T18:37:55.987Z"}]}