{"entity": "researcher", "timestamp": "2026-07-14T04:10:24.866Z", "family": "Hyrenius-Wittsten", "given": "Axel", "initials": "A", "orcid": "0000-0002-1239-4954", "affiliations": ["Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/26ee89834c8f409a9445c5b16d8f691e.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/26ee89834c8f409a9445c5b16d8f691e"}}, "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": "57c0d4d466524d61b08f72dc7b92965d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/57c0d4d466524d61b08f72dc7b92965d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/57c0d4d466524d61b08f72dc7b92965d"}}, "title": "Activating mutations remodel the chromatin accessibility landscape to drive distinct regulatory networks in KMT2A-rearranged acute leukemia.", "authors": [{"family": "Zhang", "given": "Qirui", "initials": "Q"}, {"family": "Falqu\u00e9s-Costa", "given": "Ton", "initials": "T", "orcid": "0000-0002-5341-4472", "researcher": {"href": "https://publications.scilifelab.se/researcher/a75e19f3905e45059507c43f4722da39.json"}}, {"family": "Pilheden", "given": "Mattias", "initials": "M"}, {"family": "Sturesson", "given": "Helena", "initials": "H"}, {"family": "Ovlund", "given": "Tina", "initials": "T"}, {"family": "Rissler", "given": "Vendela", "initials": "V"}, {"family": "Castor", "given": "Anders", "initials": "A"}, {"family": "Marquart", "given": "Hanne V H", "initials": "HVH"}, {"family": "Lausen", "given": "Birgitte", "initials": "B", "orcid": "0000-0002-5306-0774", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc5eadc48e354c4cb70d68d420bfa6fe.json"}}, {"family": "Fioretos", "given": "Thoas", "initials": "T"}, {"family": "Hyrenius-Wittsten", "given": "Axel", "initials": "A", "orcid": "0000-0002-1239-4954", "researcher": {"href": "https://publications.scilifelab.se/researcher/26ee89834c8f409a9445c5b16d8f691e.json"}}, {"family": "Hagstr\u00f6m-Andersson", "given": "Anna K", "initials": "AK", "orcid": "0000-0002-2904-1311", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc93a87c663d471ba64fc3be63212a89.json"}}], "type": "journal article", "published": "2024-09-00", "journal": {"title": "Hemasphere", "issn": "2572-9241", "volume": "8", "issue": "9", "pages": "e70006", "issn-l": null}, "abstract": "Activating FLT3 and RAS mutations commonly occur in leukemia with KMT2A-gene rearrangements (KMT2A-r). However, how these mutations cooperate with the KMT2A-r to remodel the epigenetic landscape is unknown. Using a retroviral acute myeloid leukemia (AML) mouse model driven by KMT2A::MLLT3, we show that FLT3 , ITDFLT3 , and N676KNRAS remodeled the chromatin accessibility landscape and associated transcriptional networks. Although the activating mutations shared a common core of chromatin changes, each mutation exhibits unique profiles with most opened peaks associating with enhancers in intronic or intergenic regions. Specifically, G12DFLT3 and N676KNRAS rewired similar chromatin and transcriptional networks, distinct from those mediated by G12DFLT3 . Motif analysis uncovered a role for the AP-1 family of transcription factors in ITDKMT2A::MLLT3 leukemia with FLT3 and N676KNRAS , whereas Runx1 and Stat5a/Stat5b were active in the presence of G12DFLT3 . Furthermore, transcriptional programs linked to immune cell regulation were activated in ITDKMT2A-r AML expressing NRAS or G12DFLT3 , and the expression of NKG2D-ligands on N676KKMT2A-r cells rendered them sensitive to CAR T cell-mediated killing. Human KMT2A-r AML cells could be pharmacologically sensitized to NKG2D-CAR T cells by treatment with the histone deacetylase inhibitor LBH589 (panobinostat) which caused upregulation of NKG2D-ligand levels. Co-treatment with LBH589 and NKG2D-CAR T cells enabled robust AML cell killing, and the strongest effect was observed for cells expressing NRAS . Finally, the results were validated and extended to acute leukemia in infancy. Combined, activating mutations induced mutation-specific changes in the epigenetic landscape, leading to changes in transcriptional programs orchestrated by specific transcription factor networks.G12D", "doi": "10.1002/hem3.70006", "pmid": "39329074", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11426354"}, {"db": "pii", "key": "HEM370006"}], "notes": [], "created": "2024-11-18T12:56:06.452Z", "modified": "2024-11-18T12:56:07.232Z"}, {"entity": "publication", "iuid": "7d8c3416d791408eb80e36578f0510e8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7d8c3416d791408eb80e36578f0510e8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7d8c3416d791408eb80e36578f0510e8"}}, "title": "FLT3N676K drives acute myeloid leukemia in a xenograft model of KMT2A-MLLT3 leukemogenesis.", "authors": [{"family": "Hyrenius-Wittsten", "given": "Axel", "initials": "A", "orcid": "0000-0002-1239-4954", "researcher": {"href": "https://publications.scilifelab.se/researcher/26ee89834c8f409a9445c5b16d8f691e.json"}}, {"family": "Pilheden", "given": "Mattias", "initials": "M"}, {"family": "Falqu\u00e9s-Costa", "given": "Antoni", "initials": "A"}, {"family": "Eriksson", "given": "Mia", "initials": "M"}, {"family": "Sturesson", "given": "Helena", "initials": "H"}, {"family": "Schneider", "given": "Pauline", "initials": "P"}, {"family": "Wander", "given": "Priscilla", "initials": "P"}, {"family": "Garcia-Ruiz", "given": "Cristian", "initials": "C", "orcid": "0000-0003-2914-7914", "researcher": {"href": "https://publications.scilifelab.se/researcher/07826d677ce449e2811d69e273becfb4.json"}}, {"family": "Liu", "given": "Jian", "initials": "J"}, {"family": "\u00c5gerstam", "given": "Helena", "initials": "H"}, {"family": "Hultquist", "given": "Anne", "initials": "A"}, {"family": "Lilljebj\u00f6rn", "given": "Henrik", "initials": "H", "orcid": "0000-0001-8703-1173", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3a75300e8c346858ce8dd8f64ecae85.json"}}, {"family": "Stam", "given": "Ronald W", "initials": "RW"}, {"family": "J\u00e4r\u00e5s", "given": "Marcus", "initials": "M"}, {"family": "Hagstr\u00f6m-Andersson", "given": "Anna K", "initials": "AK", "orcid": "0000-0002-2904-1311", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc93a87c663d471ba64fc3be63212a89.json"}}], "type": "letter", "published": "2019-09-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "33", "issue": "9", "pages": "2310-2314", "issn-l": "0887-6924"}, "abstract": null, "doi": "10.1038/s41375-019-0465-1", "pmid": "30953031", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41375-019-0465-1"}, {"db": "pmc", "key": "PMC6756218"}], "notes": [], "created": "2019-12-18T13:04:07.051Z", "modified": "2021-11-23T14:16:07.433Z"}]}