GEO series
MBNL1 hijacks a structured single-stranded distal DNA element to sustain FLT3 expression in KMT2A-rearranged leukemias
GSE263684
Homo sapiens
Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing
19 samples
2026/06/10
GPL24676
Summary
The molecular mechanisms by which KMT2A-rearranged (KMT2A-r) leukemias maintains the oncogenic FLT3 expression remain largely unclear, limiting therapeutic opportunities. Here, we identify the RNA-binding protein MBNL1 as a novel positive regulator of FLT3 by DepMap dataset exploration and combinatorial CRISPR screens. MBNL1 promotes leukemia cell survival by sustaining FLT3 expression in a KMT2A-r context-dependent manner. Mechanistically, we discover that MBNL1 recognizes a structured single-stranded DNA (ssDNA) element containing five consecutive guanines within the FLT3 enhancer, through MBNL1?s zinc finger domains and the C-terminal unstructured region.
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