{"entity": "researcher", "timestamp": "2026-06-15T18:07:12.217Z", "family": "Hein\u00e4niemi", "given": "Merja", "initials": "M", "orcid": "0000-0001-6190-3439", "affiliations": ["Institute of Biomedicine, School of Medicine, University of Eastern Finland, 70211 Kuopio, Finland."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/be7efa5a7c9a4da18b397a07ebd8d9ec.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/be7efa5a7c9a4da18b397a07ebd8d9ec"}}, "publications": [{"entity": "publication", "iuid": "11b37392972444f5998ff8f14ca156cd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/11b37392972444f5998ff8f14ca156cd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/11b37392972444f5998ff8f14ca156cd"}}, "title": "An integrative molecular map of pediatric B-cell precursor acute lymphoblastic leukemia.", "authors": [{"family": "Krali", "given": "Olga", "initials": "O", "orcid": "0000-0002-6436-9531", "researcher": {"href": "https://publications.scilifelab.se/researcher/14a6e2f99d3b4758a10af78b93777779.json"}}, {"family": "Enblad", "given": "Anna Pia", "initials": "AP"}, {"family": "Sulyaeva", "given": "Julia", "initials": "J"}, {"family": "Gogishvili", "given": "Dea", "initials": "D"}, {"family": "Lundmark", "given": "Anders", "initials": "A"}, {"family": "Harila", "given": "Arja", "initials": "A"}, {"family": "Andersson", "given": "Claes", "initials": "C"}, {"family": "Erkers", "given": "Tom", "initials": "T"}, {"family": "Hein\u00e4niemi", "given": "Merja", "initials": "M", "orcid": "0000-0001-6190-3439", "researcher": {"href": "https://publications.scilifelab.se/researcher/be7efa5a7c9a4da18b397a07ebd8d9ec.json"}}, {"family": "L\u00f6nnerholm", "given": "Gudmar", "initials": "G"}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}], "type": "journal article", "published": "2026-04-11", "journal": {"title": "Commun Med (Lond)", "issn": "2730-664X", "volume": "6", "issue": "1", "issn-l": null}, "abstract": "The molecular landscape of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has been extensively characterized through single-modality studies. However, the interplay between molecular modalities and their collective influence on treatment response and outcomes remains poorly understood.\n\nWe integrated genomic, epigenomic, transcriptomic, and ex vivo drug response data from 1231 patients diagnosed with BCP-ALL. Using Multi-Omics Factor Analysis, we identified signatures explaining key aspects of the integrative molecular landscape, referred to as cross-modal elements (CMEs). The CME-derived signatures were introduced into pathway and intermodal network analyses, while their impact on patient outcomes was assessed through survival modeling.\n\nPathway and network analyses annotate the resulting integrative CMEs, linking them to key biological processes, including disease development, cellular regulatory processes, metabolic pathways, and drug response. By leveraging correlations between DNA methylation and ex vivo response to doxorubicin, we stratify patients with hyperdiploidy into subgroups that differ in relapse-free survival. These signatures are independent of clinical variables. Survival models incorporating CME-selected ex-vivo drug responses combined with clinical data improve risk prediction compared to clinical models alone (FDR < 0.05), demonstrating the potential of integrative multiomics in refining risk stratification.\n\nOur study highlights the importance of multimodal data integration in BCP-ALL to provide biological insights with potential relevance for precision medicine.", "doi": "10.1038/s43856-026-01568-9", "pmid": "41965886", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Short read": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13079846"}, {"db": "pii", "key": "10.1038/s43856-026-01568-9"}], "notes": [], "created": "2026-06-01T11:13:50.747Z", "modified": "2026-06-01T11:13:50.765Z"}, {"entity": "publication", "iuid": "2cac753de106445cbf229064ef982197", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2cac753de106445cbf229064ef982197.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2cac753de106445cbf229064ef982197"}}, "title": "Genomic determinants of therapy response in ETV6::RUNX1 leukemia.", "authors": [{"family": "Oksa", "given": "Laura", "initials": "L", "orcid": "0000-0003-4468-9877", "researcher": {"href": "https://publications.scilifelab.se/researcher/5526f0f44427441bb2a49f27f00b5683.json"}}, {"family": "Moisio", "given": "Sanni", "initials": "S", "orcid": "0009-0009-4446-015X", "researcher": {"href": "https://publications.scilifelab.se/researcher/de1112350e9042bfa9a8707d2c255bf5.json"}}, {"family": "Maqbool", "given": "Khurram", "initials": "K", "orcid": "0000-0003-2981-2582", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ea06b85057744018f754c373fef3ca5.json"}}, {"family": "Kramer", "given": "Roger", "initials": "R"}, {"family": "Nikkil\u00e4", "given": "Atte", "initials": "A"}, {"family": "Jayasingha", "given": "Buddika", "initials": "B"}, {"family": "M\u00e4kinen", "given": "Artturi", "initials": "A", "orcid": "0000-0002-5521-9216", "researcher": {"href": "https://publications.scilifelab.se/researcher/74542e2da6d542d8a40b93b692c7b760.json"}}, {"family": "Foroughi-Asl", "given": "Hassan", "initials": "H"}, {"family": "Rounioja", "given": "Samuli", "initials": "S"}, {"family": "Suhonen", "given": "Janne", "initials": "J"}, {"family": "Krali", "given": "Olga", "initials": "O", "orcid": "0000-0002-6436-9531", "researcher": {"href": "https://publications.scilifelab.se/researcher/14a6e2f99d3b4758a10af78b93777779.json"}}, {"family": "Voutilainen", "given": "Miikka", "initials": "M", "orcid": "0000-0001-9367-3471", "researcher": {"href": "https://publications.scilifelab.se/researcher/390e63751ebb46e3873d801ce0c620d1.json"}}, {"family": "Lahnalampi", "given": "Mari", "initials": "M", "orcid": "0000-0003-4050-4935", "researcher": {"href": "https://publications.scilifelab.se/researcher/31d154912d9f4b9ca680f9d019035d46.json"}}, {"family": "Veps\u00e4l\u00e4inen", "given": "Kaisa", "initials": "K"}, {"family": "Huang", "given": "Sui", "initials": "S"}, {"family": "Duque-Afonso", "given": "Jesus", "initials": "J", "orcid": "0000-0002-8287-5673", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc78f208850b4a999859f110a3850bfa.json"}}, {"family": "Hauer", "given": "Julia", "initials": "J", "orcid": "0000-0002-4058-3058", "researcher": {"href": "https://publications.scilifelab.se/researcher/9387a9c586f74172a9d251fff4d71637.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Lohi", "given": "Olli", "initials": "O", "orcid": "0000-0001-9195-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/e11a59310dfc40e6a111367914fdba9e.json"}}, {"family": "Hein\u00e4niemi", "given": "Merja", "initials": "M", "orcid": "0000-0001-6190-3439", "researcher": {"href": "https://publications.scilifelab.se/researcher/be7efa5a7c9a4da18b397a07ebd8d9ec.json"}}], "type": "journal article", "published": "2025-09-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "issn-l": "0887-6924", "volume": "39", "issue": "9", "pages": "2125-2139"}, "abstract": "ETV6::RUNX1 leukemia is the second most common subtype of childhood B cell acute lymphoblastic leukemia (B-ALL). Although it generally has a low relapse risk, a significant proportion of B-ALL relapses occur within this subtype due to its relatively high incidence. Measurable residual disease at the end of induction therapy is a well-established biomarker predicting treatment outcomes, while no genomic biomarkers are routinely applied in clinics. In this study, we used multiomic data from ETV6::RUNX1 leukemias to identify genomic features predictive of therapy response at disease presentation. In the deeply characterized sub-cohort we discovered that fast-responding cases frequently exhibited the APOBEC mutational signature and the gene expression signature of high cell cycle activity. In contrast, rearrangements of IGK genes were more frequent in slow responders. Additionally, response-related mutations were identified in transcriptional regulators and tumor suppressor genes (INTS1, NF1, TP53). Copy number analysis revealed that fast responders harbored more frequent deletions of chr12 p-arm, leading to transcriptomic changes affecting genes associated with induction therapy response (KRAS, FKBP4), while a shorter gain in chr12 was more common in slow responders. The identified genetic and transcriptomic markers of treatment sensitivity pave the way for improved disease classification at presentation, potentially improving clinical outcomes.", "doi": "10.1038/s41375-025-02683-7", "pmid": "40634509", "labels": {"NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "NGI Short read": "Service", "Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12380598"}, {"db": "pii", "key": "10.1038/s41375-025-02683-7"}], "notes": [], "created": "2025-09-08T11:39:55.025Z", "modified": "2025-11-18T20:46:15.313Z"}, {"entity": "publication", "iuid": "31cc2ec2f8a34c93b6d17050bec2d830", "links": {"self": {"href": "https://publications.scilifelab.se/publication/31cc2ec2f8a34c93b6d17050bec2d830.json"}, "display": {"href": "https://publications.scilifelab.se/publication/31cc2ec2f8a34c93b6d17050bec2d830"}}, "title": "Single-cell analysis of aplastic anemia reveals a convergence of NK and NK-like CD8+ T cells with a disease-associated TCR signature.", "authors": [{"family": "Lundgren", "given": "Sofie", "initials": "S", "orcid": "0000-0003-3146-9816", "researcher": {"href": "https://publications.scilifelab.se/researcher/3838050baa4847c5ad8edcd02b3b54e2.json"}}, {"family": "Huuhtanen", "given": "Jani", "initials": "J", "orcid": "0000-0003-2750-4033", "researcher": {"href": "https://publications.scilifelab.se/researcher/f982fef263e644799e27df3f31083d6c.json"}}, {"family": "Ker\u00e4nen", "given": "Mikko", "initials": "M", "orcid": "0000-0001-8027-499X", "researcher": {"href": "https://publications.scilifelab.se/researcher/065055dc206c4749b64c08e7414875b1.json"}}, {"family": "Feng", "given": "Xingmin", "initials": "X", "orcid": "0000-0001-8018-2366", "researcher": {"href": "https://publications.scilifelab.se/researcher/ecf564243b464d919b534c054c6e5fee.json"}}, {"family": "Patel", "given": "Bhavisha A", "initials": "BA", "orcid": "0000-0002-2974-7701", "researcher": {"href": "https://publications.scilifelab.se/researcher/8f42376804c4437fb68895915f369d39.json"}}, {"family": "Ryland", "given": "Georgina L", "initials": "GL", "orcid": "0000-0002-4990-0961", "researcher": {"href": "https://publications.scilifelab.se/researcher/891952aec8b442e1af79388838e73e05.json"}}, {"family": "Fox", "given": "Lucy C", "initials": "LC", "orcid": "0000-0002-3855-8232", "researcher": {"href": "https://publications.scilifelab.se/researcher/827f9263f0734c7ab1b757bc35758862.json"}}, {"family": "Bravo-Perez", "given": "Carlos", "initials": "C", "orcid": "0000-0001-9794-7847", "researcher": {"href": "https://publications.scilifelab.se/researcher/4260758112534ceba7efe94660a0a43e.json"}}, {"family": "Clemente", "given": "Michael", "initials": "M"}, {"family": "Kerr", "given": "Cassandra", "initials": "C"}, {"family": "Walldin", "given": "Gunilla", "initials": "G", "orcid": "0009-0005-6663-6540", "researcher": {"href": "https://publications.scilifelab.se/researcher/24fb888d0212421eaa2353ed6cc31ac7.json"}}, {"family": "Dufva", "given": "Olli", "initials": "O"}, {"family": "Zaimoku", "given": "Yoshitaka", "initials": "Y", "orcid": "0000-0002-4108-5245", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9bc97e77a35491197fa901757bd92f0.json"}}, {"family": "Tuononen", "given": "Tiina", "initials": "T", "orcid": "0009-0007-6677-3064", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2c764c4bf7746fc9c6c468a51a5db52.json"}}, {"family": "Myllym\u00e4ki", "given": "Mikko", "initials": "M", "orcid": "0000-0002-8194-7356", "researcher": {"href": "https://publications.scilifelab.se/researcher/071c21748567437393dfb1b7c3bedad4.json"}}, {"family": "Ebeling", "given": "Freja", "initials": "F", "orcid": "0000-0002-7921-089X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5318f08e1aff4e988f961f1c7806d1bb.json"}}, {"family": "Jokinen", "given": "Emmi", "initials": "E", "orcid": "0000-0002-0060-6868", "researcher": {"href": "https://publications.scilifelab.se/researcher/8392afc052914d47ab93466ba898cbc8.json"}}, {"family": "Heinonen", "given": "Markus", "initials": "M", "orcid": "0000-0002-7741-2279", "researcher": {"href": "https://publications.scilifelab.se/researcher/8733ddf664b2445188aed518dab08873.json"}}, {"family": "Kasanen", "given": "Tiina", "initials": "T", "orcid": "0000-0002-5408-1948", "researcher": {"href": "https://publications.scilifelab.se/researcher/06fb270832244566bfc649d43f7e718c.json"}}, {"family": "Klievink", "given": "Jay", "initials": "J", "orcid": "0000-0002-4081-5840", "researcher": {"href": "https://publications.scilifelab.se/researcher/fdad6fd259c749a5b3a770ae47c770cf.json"}}, {"family": "L\u00e4hteenm\u00e4ki", "given": "Hanna", "initials": "H", "orcid": "0000-0001-6773-2677", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0cb9da3e4cb4430a779d4d4185e6652.json"}}, {"family": "Jaatinen", "given": "Taina", "initials": "T", "orcid": "0000-0001-7783-6189", "researcher": {"href": "https://publications.scilifelab.se/researcher/3b981dc2e49a4731abc5ac1ee7bbfecf.json"}}, {"family": "Kyt\u00f6l\u00e4", "given": "Sari", "initials": "S", "orcid": "0000-0003-1649-8993", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8e0b29c15c24626b529b3b1cab1ca1a.json"}}, {"family": "Siitonen", "given": "Sanna", "initials": "S", "orcid": "0009-0001-2241-6731", "researcher": {"href": "https://publications.scilifelab.se/researcher/5c6a7c0c04f3451086c3b32d74da6ffa.json"}}, {"family": "Dulau-Florea", "given": "Alina", "initials": "A", "orcid": "0000-0003-3512-4946", "researcher": {"href": "https://publications.scilifelab.se/researcher/480fa59b41ab400d8eca304bf23c3332.json"}}, {"family": "Braylan", "given": "Raul", "initials": "R", "orcid": "0000-0001-6733-5161", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1ec596e60c542238a5ada29bb62fc51.json"}}, {"family": "Hein\u00e4niemi", "given": "Merja", "initials": "M", "orcid": "0000-0001-6190-3439", "researcher": {"href": "https://publications.scilifelab.se/researcher/be7efa5a7c9a4da18b397a07ebd8d9ec.json"}}, {"family": "Nakao", "given": "Shinji", "initials": "S", "orcid": "0000-0002-9674-624X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab2d147043454ff2b403f70bd60136e6.json"}}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E", "orcid": "0000-0002-7839-3743", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bf8d52e24234fa8b348ad08f58d1d48.json"}}, {"family": "Maciejewski", "given": "Jaroslaw P", "initials": "JP"}, {"family": "Blombery", "given": "Piers", "initials": "P"}, {"family": "Young", "given": "Neal S", "initials": "NS"}, {"family": "L\u00e4hdesm\u00e4ki", "given": "Harri", "initials": "H"}, {"family": "Mustjoki", "given": "Satu", "initials": "S", "orcid": "0000-0002-0816-8241", "researcher": {"href": "https://publications.scilifelab.se/researcher/03cdbac477284e7093121bc3d35a6dfb.json"}}], "type": "journal article", "published": "2025-02-26", "journal": {"title": "Sci Transl Med", "issn": "1946-6242", "volume": "17", "issue": "787", "pages": "eadl6758", "issn-l": "1946-6234"}, "abstract": "Immune aplastic anemia (AA) is a life-threatening bone marrow failure disorder driven by an autoimmune T cell attack against hematopoietic stem and progenitor cells (HSPCs). However, the exact autoantigen targets and role of other immune cells in the pathogenesis of AA are unknown. Here, we analyzed a cohort of 218 patients with AA using single-cell RNA and T cell receptor (TCR) \u03b1\u03b2 sequencing, TCR\u03b2 sequencing, flow cytometry, and plasma cytokine profiling. We identified natural killer (NK) cells and CD8+ terminally differentiated effector T (TEMRA) cells expressing NK receptors with AA-associated TCR\u03b2 motifs as the most dysregulated immune cell populations in AA bone marrow. Functional coculture experiments using primary HSPCs and immune cells showed that NK cells cannot kill HSPCs alone but may sensitize HSPCs to CD8+ T cell-mediated killing through production of interferons. Furthermore, HSPCs induced activation of T cell clones with CD8+ TEMRA NK-like phenotype in coculture. Our results reveal a convergent phenotype of innate and adaptive immune cells that may drive AA.", "doi": "10.1126/scitranslmed.adl6758", "pmid": "40009697", "labels": {"NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [], "notes": [], "created": "2025-09-08T11:37:23.304Z", "modified": "2025-09-08T11:37:24.704Z"}, {"entity": "publication", "iuid": "a38bcd8983b6490d907efb63b0437778", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a38bcd8983b6490d907efb63b0437778.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a38bcd8983b6490d907efb63b0437778"}}, "title": "Sequential drug treatment targeting cell cycle and cell fate regulatory programs blocks non-genetic cancer evolution in acute lymphoblastic leukemia.", "authors": [{"family": "Malyukova", "given": "Alena", "initials": "A"}, {"family": "Lahnalampi", "given": "Mari", "initials": "M"}, {"family": "Falqu\u00e9s-Costa", "given": "Ton", "initials": "T"}, {"family": "P\u00f6l\u00f6nen", "given": "Petri", "initials": "P"}, {"family": "Sipola", "given": "Mikko", "initials": "M"}, {"family": "Mehtonen", "given": "Juha", "initials": "J"}, {"family": "Teppo", "given": "Susanna", "initials": "S"}, {"family": "Akopyan", "given": "Karen", "initials": "K"}, {"family": "Viiliainen", "given": "Johanna", "initials": "J"}, {"family": "Lohi", "given": "Olli", "initials": "O"}, {"family": "Hagstr\u00f6m-Andersson", "given": "Anna K", "initials": "AK"}, {"family": "Hein\u00e4niemi", "given": "Merja", "initials": "M", "orcid": "0000-0001-6190-3439", "researcher": {"href": "https://publications.scilifelab.se/researcher/be7efa5a7c9a4da18b397a07ebd8d9ec.json"}}, {"family": "Sangfelt", "given": "Olle", "initials": "O"}], "type": "journal article", "published": "2024-05-31", "journal": {"title": "Genome Biol.", "issn": "1474-760X", "volume": "25", "issue": "1", "pages": "143", "issn-l": "1474-7596"}, "abstract": "Targeted therapies exploiting vulnerabilities of cancer cells hold promise for improving patient outcome and reducing side-effects of chemotherapy. However, efficacy of precision therapies is limited in part because of tumor cell heterogeneity. A better mechanistic understanding of how drug effect is linked to cancer cell state diversity is crucial for identifying effective combination therapies that can prevent disease recurrence.\n\nHere, we characterize the effect of G2/M checkpoint inhibition in acute lymphoblastic leukemia (ALL) and demonstrate that WEE1 targeted therapy impinges on cell fate decision regulatory circuits. We find the highest inhibition of recovery of proliferation in ALL cells with KMT2A-rearrangements. Single-cell RNA-seq and ATAC-seq of RS4;11 cells harboring KMT2A::AFF1, treated with the WEE1 inhibitor AZD1775, reveal diversification of cell states, with a fraction of cells exhibiting strong activation of p53-driven processes linked to apoptosis and senescence, and disruption of a core KMT2A-RUNX1-MYC regulatory network. In this cell state diversification induced by WEE1 inhibition, a subpopulation transitions to a drug tolerant cell state characterized by activation of transcription factors regulating pre-B cell fate, lipid metabolism, and pre-BCR signaling in a reversible manner. Sequential treatment with BCR-signaling inhibitors dasatinib, ibrutinib, or perturbing metabolism by fatostatin or AZD2014 effectively counteracts drug tolerance by inducing cell death and repressing stemness markers.\n\nCollectively, our findings provide new insights into the tight connectivity of gene regulatory programs associated with cell cycle and cell fate regulation, and a rationale for sequential administration of WEE1 inhibitors with low toxicity inhibitors of pre-BCR signaling or metabolism.", "doi": "10.1186/s13059-024-03260-4", "pmid": "38822412", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11143599"}, {"db": "pii", "key": "10.1186/s13059-024-03260-4"}], "notes": [], "created": "2024-11-18T12:54:45.211Z", "modified": "2024-11-18T12:54:45.439Z"}, {"entity": "publication", "iuid": "b5e506c4f52f4719b99d056ffc5fb4eb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b5e506c4f52f4719b99d056ffc5fb4eb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b5e506c4f52f4719b99d056ffc5fb4eb"}}, "title": "Genome-wide repression of eRNA and target gene loci by the ETV6-RUNX1 fusion in acute leukemia.", "authors": [{"family": "Teppo", "given": "Susanna", "initials": "S", "orcid": "0000-0003-2569-8030", "researcher": {"href": "https://publications.scilifelab.se/researcher/645b5398a7144dab9630f882e572b61b.json"}}, {"family": "Laukkanen", "given": "Saara", "initials": "S"}, {"family": "Liuksiala", "given": "Thomas", "initials": "T"}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Oittinen", "given": "Mikko", "initials": "M"}, {"family": "Teittinen", "given": "Kaisa", "initials": "K"}, {"family": "Gr\u00f6nroos", "given": "Toni", "initials": "T"}, {"family": "St-Onge", "given": "Pascal", "initials": "P"}, {"family": "Sinnett", "given": "Daniel", "initials": "D"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Nykter", "given": "Matti", "initials": "M"}, {"family": "Viiri", "given": "Keijo", "initials": "K"}, {"family": "Hein\u00e4niemi", "given": "Merja", "initials": "M", "orcid": "0000-0001-6190-3439", "researcher": {"href": "https://publications.scilifelab.se/researcher/be7efa5a7c9a4da18b397a07ebd8d9ec.json"}}, {"family": "Lohi", "given": "Olli", "initials": "O", "orcid": "0000-0001-9195-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/e11a59310dfc40e6a111367914fdba9e.json"}}], "type": "journal article", "published": "2016-11-00", "journal": {"volume": "26", "issn": "1549-5469", "issue": "11", "pages": "1468-1477", "title": "Genome Res.", "issn-l": "1088-9051"}, "abstract": "Approximately 20%-25% of childhood acute lymphoblastic leukemias carry the ETV6-RUNX1 (E/R) fusion gene, a fusion of two central hematopoietic transcription factors, ETV6 (TEL) and RUNX1 (AML1). Despite its prevalence, the exact genomic targets of E/R have remained elusive. We evaluated gene loci and enhancers targeted by E/R genome-wide in precursor B acute leukemia cells using global run-on sequencing (GRO-seq). We show that expression of the E/R fusion leads to widespread repression of RUNX1 motif-containing enhancers at its target gene loci. Moreover, multiple super-enhancers from the CD19+/CD20+-lineage were repressed, implicating a role in impediment of lineage commitment. In effect, the expression of several genes involved in B cell signaling and adhesion was down-regulated, and the repression depended on the wild-type DNA-binding Runt domain of RUNX1. We also identified a number of E/R-regulated annotated and de novo noncoding genes. The results provide a comprehensive genome-wide mapping between E/R-regulated key regulatory elements and genes in precursor B cell leukemia that disrupt normal B lymphopoiesis.", "doi": "10.1101/gr.193649.115", "pmid": "27620872", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "gr.193649.115"}, {"db": "pmc", "key": "PMC5088590"}], "notes": [], "created": "2017-05-03T13:00:09.806Z", "modified": "2024-01-16T13:48:49.020Z"}]}