{"entity": "researcher", "timestamp": "2026-08-28T00:52:18.773Z", "family": "Post", "given": "Frederik", "initials": "F", "orcid": "0000-0003-0376-1326", "affiliations": ["Department of Oncology-Pathology, Clinical Proteomics Mass Spectrometry, Karolinska Institutet, Science for Life Laboratory, Solna, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/46a4e396bc7645b893eeadb97a92e49f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/46a4e396bc7645b893eeadb97a92e49f"}}, "publications": [{"entity": "publication", "iuid": "b3628ae9e7e34f74b3621b09352d50d2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b3628ae9e7e34f74b3621b09352d50d2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b3628ae9e7e34f74b3621b09352d50d2"}}, "title": "Preclinical efficacy of azacitidine and venetoclax for infant KMT2A-rearranged acute lymphoblastic leukemia reveals a new therapeutic strategy.", "authors": [{"family": "Cheung", "given": "Laurence C", "initials": "LC", "orcid": "0000-0001-6298-5288", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6d252d339ea54457b0ac661ef6bee69e.json"}}, {"family": "Aya-Bonilla", "given": "Carlos", "initials": "C"}, {"family": "Cruickshank", "given": "Mark N", "initials": "MN", "orcid": "0000-0002-1869-1175", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc8e82d19bf2428f9bdbdd339c7bfd04.json"}}, {"family": "Chiu", "given": "Sung K", "initials": "SK", "orcid": "0000-0002-7230-6442", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bb9afe24f4a0472d9a1ca7115bf3a0d0.json"}}, {"family": "Kuek", "given": "Vincent", "initials": "V", "orcid": "0000-0003-2225-8566", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/da77d1a8b19540a8864315cf15c4eba3.json"}}, {"family": "Anderson", "given": "Denise", "initials": "D"}, {"family": "Chua", "given": "Grace-Alyssa", "initials": "GA"}, {"family": "Singh", "given": "Sajla", "initials": "S"}, {"family": "Oommen", "given": "Joyce", "initials": "J"}, {"family": "Ferrari", "given": "Emanuela", "initials": "E"}, {"family": "Hughes", "given": "Anastasia M", "initials": "AM"}, {"family": "Ford", "given": "Jette", "initials": "J"}, {"family": "Kunold", "given": "Elena", "initials": "E"}, {"family": "Hesselman", "given": "Maria C", "initials": "MC", "orcid": "0000-0003-4858-6920", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e8057bca2f4d4884a7b038a9d2ac6b90.json"}}, {"family": "Post", "given": "Frederik", "initials": "F", "orcid": "0000-0003-0376-1326", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/46a4e396bc7645b893eeadb97a92e49f.json"}}, {"family": "Faulk", "given": "Kelly E", "initials": "KE"}, {"family": "Breese", "given": "Erin H", "initials": "EH"}, {"family": "Guest", "given": "Erin M", "initials": "EM", "orcid": "0000-0003-2482-5608", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d8ff46e2c76649d9b0cb25742d10df8a.json"}}, {"family": "Brown", "given": "Patrick A", "initials": "PA", "orcid": "0000-0002-8653-1069", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f5f09548f41c43c48625fbb419be00cc.json"}}, {"family": "Loh", "given": "Mignon L", "initials": "ML"}, {"family": "Lock", "given": "Richard B", "initials": "RB"}, {"family": "Kees", "given": "Ursula R", "initials": "UR"}, {"family": "Jafari", "given": "Rozbeh", "initials": "R", "orcid": "0000-0002-3396-4709", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/95546f158dde40709fbfbb822a8f89c5.json"}}, {"family": "Malinge", "given": "S\u00e9bastien", "initials": "S", "orcid": "0000-0002-9533-7778", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9bdad6f9777b4d1db716a65602591133.json"}}, {"family": "Kotecha", "given": "Rishi S", "initials": "RS", "orcid": "0000-0003-1836-4075", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/84afb00f1e944bad871c8481eebc24bb.json"}}], "type": "journal article", "published": "2023-01-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "37", "issue": "1", "pages": "61-71", "issn-l": "0887-6924"}, "abstract": "Infants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL) have a dismal prognosis. Survival outcomes have remained static in recent decades despite treatment intensification and novel therapies are urgently required. KMT2A-rearranged infant ALL cells are characterized by an abundance of promoter hypermethylation and exhibit high BCL-2 expression, highlighting potential for therapeutic targeting. Here, we show that hypomethylating agents exhibit in vitro additivity when combined with most conventional chemotherapeutic agents. However, in a subset of samples an antagonistic effect was seen between several agents. This was most evident when hypomethylating agents were combined with methotrexate, with upregulation of ATP-binding cassette transporters identified as a potential mechanism. Single agent treatment with azacitidine and decitabine significantly prolonged in vivo survival in KMT2A-rearranged infant ALL xenografts. Treatment of KMT2A-rearranged infant ALL cell lines with azacitidine and decitabine led to differential genome-wide DNA methylation, changes in gene expression and thermal proteome profiling revealed the target protein-binding landscape of these agents. The selective BCL-2 inhibitor, venetoclax, exhibited in vitro additivity in combination with hypomethylating or conventional chemotherapeutic agents. The addition of venetoclax to azacitidine resulted in a significant in vivo survival advantage indicating the therapeutic potential of this combination to improve outcome for infants with KMT2A-rearranged ALL.", "doi": "10.1038/s41375-022-01746-3", "pmid": "36380143", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9883157"}, {"db": "pii", "key": "10.1038/s41375-022-01746-3"}], "notes": [], "created": "2026-08-21T11:46:55.691Z", "modified": "2026-08-21T11:46:56.132Z"}]}