Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia

Lauren V. Cairns, Katrina M. Lappin, Alexander Mutch, Ahlam Ali, Kyle B. Matchett, Ken I. Mills

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article numbere10163
JournalInternational Journal of Molecular Sciences
Volume22
Issue number18
Early online date21 Sep 2021
DOIs
Publication statusE-pub ahead of print - 21 Sep 2021

Keywords

  • acute myeloid leukaemia
  • paediatric
  • drug repurposing
  • multiplex screening

Fingerprint

Dive into the research topics of 'Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia'. Together they form a unique fingerprint.

Cite this