{"entity": "researcher", "timestamp": "2026-08-20T21:24:15.821Z", "family": "Hormann", "given": "Femke M", "initials": "FM", "orcid": "0000-0001-5164-3047", "affiliations": ["Science for Life Laboratory (SciLifeLab), Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/8868b55d9ca345f5b92aff76547e0e7c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/8868b55d9ca345f5b92aff76547e0e7c"}}, "publications": [{"entity": "publication", "iuid": "e8a7f3c98b344f20863ac4cd24bd5507", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e8a7f3c98b344f20863ac4cd24bd5507.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e8a7f3c98b344f20863ac4cd24bd5507"}}, "title": "Nelarabine in T-cell acute lymphoblastic leukemia: intracellular metabolism and molecular mode-of-action.", "authors": [{"family": "Hormann", "given": "Femke M", "initials": "FM", "orcid": "0000-0001-5164-3047", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8868b55d9ca345f5b92aff76547e0e7c.json"}}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d65643e96cfe4f3a98cf4f48225eac73.json"}}], "type": "journal article", "published": "2025-03-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "39", "issue": "3", "pages": "531-542", "issn-l": "0887-6924"}, "abstract": "T-cell acute lymphoblastic leukemia (T-ALL) patients often have a poor 5-year event-free survival. The only T-ALL specific drug in clinical practice is nelarabine. A prodrug of the deoxyguanosine analog ara-G, nelarabine is a rationally designed agent selective for the treatment of T-cell malignancies. Originally approved for relapsed/refractory T-ALL, it is increasingly used in T-ALL therapy and is currently being evaluated in upfront treatment. Whilst the clinical use of nelarabine has been the topic of multiple review articles, a thorough overview of the preclinical data detailing the molecular underpinnings of its anti-leukemic activity is lacking, which is critical to inform mechanism-based use. Thus, in the present article we conducted a semi-systematic review of the literature and critically evaluated the preclinical knowledge on the molecular pharmacology of nelarabine. Whilst early studies identified ara-G triphosphate to be the principal active metabolite and nuclear DNA synthesis to be a key target, many fundamental questions remain that could inform upon future use of this therapy. These include the nature of nelarabine-induced DNA lesions and their repair, together with additional cellular targets of ara-G metabolites and their role in efficacy and toxicity. A critical avenue of research in need of development is investigation of nelarabine combination therapies, both in the context of current T-ALL chemotherapy regimens and with emerging anti-leukemic agents, and we highlight some areas to pursue. Altogether, we discuss what we can learn from the preclinical literature as a whole and present our view for future research regarding nelarabine treatment in T-ALL.", "doi": "10.1038/s41375-025-02529-2", "pmid": "39962329", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11879874"}, {"db": "pii", "key": "10.1038/s41375-025-02529-2"}], "notes": [], "created": "2026-08-20T08:47:23.157Z", "modified": "2026-08-20T08:47:49.089Z"}]}