Klin Padiatr 2022; 234(03): 175
DOI: 10.1055/s-0042-1748683
Abstracts

Novel therapeutic avenues for MLL-AF4+ pro-B ALL patients based on a unique microRNA expression signature

C Malouf
1   Centre for Regenerative Medicine, The University of Edinburgh, United Kingdom
,
A Duguid
1   Centre for Regenerative Medicine, The University of Edinburgh, United Kingdom
,
K Ottersbach
1   Centre for Regenerative Medicine, The University of Edinburgh, United Kingdom
› Author Affiliations
 

MLL-AF4+ infant leukemia patients have a unique microRNA expression signature that can be used to understand leukemogenesis and to identify novel therapeutic avenues. We have previously shown that miR-128a and miR-130b, which are upregulated in patients, act as essential lineage-specific co-drivers of MLL-AF4+ leukemia (PMID: 34111240). Our most recent and unpublished work now focuses on three additional microRNAs that are downregulated in MLL-AF4+ pro-B ALL patients: miR-194, miR-99b and miR-125a-5p. The overexpression of all three microRNAs decreased the survival of MLL-AF4+ leukemic blasts and impaired the maintenance of MLL-AF4+ pro-B ALL in mice, indicating that they act as tumour suppressors. Downstream of these, we identified CA5B (miR-194 target), PPP3CA (miR-99b target) and PPP2R5C (miR-125a-5p target) that are upregulated in patients and targeted by Diamox, FK506 and LB-100, respectively. Importantly, in vivo treatment with these drugs reduced the leukemia burden of MLL-AF4+ pro-B ALL mice. Future studies will focus on assessing the drug repurposing potential of Diamox, FK506 and LB-100 for the treatment of MLL-AF4+ pro-B ALL patients.



Publication History

Article published online:
17 May 2022

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