Related Experiment Video

Updated: Apr 28, 2026

Author Spotlight: Advancing the Detection of Low-Frequency Mutations in Cancer Tissues
07:17

Author Spotlight: Advancing the Detection of Low-Frequency Mutations in Cancer Tissues

Published on: August 23, 2024

1.8K

A microRNA expression signature in infant t(4;11) KMT2A::AFF1+ BCP-ALL uncovers novel therapeutic targets

Camille Malouf1, Alasdair Duguid1, Kirsten S Vrenken2

  • 1Centre for Regenerative Medicine, Institute for Regeneration and Repair University of Edinburgh Edinburgh UK.

Hemasphere
|April 27, 2026
PubMed

Insights

Three microRNAs (miR-194, miR-99b, miR-125a-5p) show promise in treating KMT2A::AFF1+ B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Drug repurposing targeting their upregulated genes reduced leukemia burden in vivo, offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Infants and children with KMT2A::AFF1+ leukemia face poor prognoses, necessitating novel therapies.
  • MicroRNAs play crucial roles in cancer development and progression.

Purpose of the Study:

  • To investigate the role of downregulated microRNAs (miR-194, miR-99b, miR-125a-5p) in KMT2A::AFF1+ B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
  • To identify therapeutic targets and explore drug repurposing for KMT2A::AFF1+ BCP-ALL.

Main Methods:

  • Overexpression of miR-194, miR-99b, and miR-125a-5p in KMT2A::AFF1+ BCP-ALL cells.
  • Identification of upregulated microRNA target genes (CA5B, PPP3CA, PPP2R5C) in KMT2A::AFF1+ BCP-ALL.
  • Drug repurposing screen using acetazolamide, tacrolimus, and LB-100 to inhibit target genes.
  • In vivo studies using patient-derived xenotransplant models.

Main Results:

  • Overexpression of the three microRNAs reduced KMT2A::AFF1+ leukemic blast survival and BCP-ALL maintenance.
  • Inhibition of CA5B, PPP3CA, and PP2A by repurposed drugs demonstrated high toxicity against KMT2A::AFF1+ leukemic blasts.
  • Acetazolamide reduced leukemia burden in vivo and prolonged survival in patient-derived xenotransplant models when combined with standard therapy.

Conclusions:

  • The unique microRNA signature in KMT2A::AFF1+ BCP-ALL can identify novel therapeutic targets.
  • Drug repurposing of acetazolamide, tacrolimus, and LB-100 shows potential for treating KMT2A::AFF1+ BCP-ALL.
  • Combination therapy with repurposed drugs may offer a less toxic treatment approach for infant ALL.

More Related Videos

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

7.6K
Mapping Infant Immunity with Minimal Input: Integrative Single-cell and Multiomic Profiling09:04

Mapping Infant Immunity with Minimal Input: Integrative Single-cell and Multiomic Profiling

Published on: April 3, 2026

97

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
20.9K