{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:22:56Z","timestamp":1760235776080,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the malignant transformation of myeloid precursor cells with impaired differentiation. Standard therapy for paediatric AML has remained largely unchanged for over four decades and, combined with inadequate understanding of the biology of paediatric AML, has limited the progress of targeted therapies in this cohort. In recent years, the search for novel targets for the treatment of paediatric AML has accelerated in parallel with advanced genomic technologies which explore the mutational and transcriptional landscape of this disease. Exploiting the large combinatorial space of existing drugs provides an untapped resource for the identification of potential combination therapies for the treatment of paediatric AML. We have previously designed a multiplex screening strategy known as Multiplex Screening for Interacting Compounds in AML (MuSICAL); using an algorithm designed in-house, we screened all pairings of 384 FDA-approved compounds in less than 4000 wells by pooling drugs into 10 compounds per well. This approach maximised the probability of identifying new compound combinations with therapeutic potential while minimising cost, replication and redundancy. This screening strategy identified the triple combination of glimepiride, a sulfonylurea; pancuronium dibromide, a neuromuscular blocking agent; and vinblastine sulfate, a vinca alkaloid, as a potential therapy for paediatric AML. We envision that this approach can be used for a variety of disease-relevant screens allowing the efficient repurposing of drugs that can be rapidly moved into the clinic.<\/jats:p>","DOI":"10.3390\/ijms221810163","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T08:04:23Z","timestamp":1632211463000},"page":"10163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia"],"prefix":"10.3390","volume":"22","author":[{"given":"Lauren V.","family":"Cairns","sequence":"first","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina M.","family":"Lappin","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Mutch","sequence":"additional","affiliation":[{"name":"Northern Ireland Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, C-TRIC, Altnagelvin Hospital Campus, Glenshane Road, Derry\/Londonderry BT47 6SB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahlam","family":"Ali","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle B.","family":"Matchett","sequence":"additional","affiliation":[{"name":"Northern Ireland Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, C-TRIC, Altnagelvin Hospital Campus, Glenshane Road, Derry\/Londonderry BT47 6SB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-4481","authenticated-orcid":false,"given":"Ken I.","family":"Mills","sequence":"additional","affiliation":[{"name":"Patrick G. Johnston Centre for Cancer Research, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kellaway, S., Chin, P.S., Barneh, F., Bonifer, C., and Heidenreich, O. (2020). t(8;21) Acute Myeloid Leukemia as a Paradigm for the Understanding of Leukemogenesis at the Level of Gene Regulation and Chromatin Programming. Cells, 9.","DOI":"10.3390\/cells9122681"},{"key":"ref_2","first-page":"1","article-title":"Targeting multiple signaling pathways: The new approach to acute myeloid leukemia therapy","volume":"5","author":"Carter","year":"2020","journal-title":"Signal Transduct. Target. 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