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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 Submitted 2026/06/10 Platform 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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Direct links to NCBI, no account and no request form: the whole study as GSE263684_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 19 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1098737 and SRA study SRP500815. Searching any of these in the dataset finder brings you back here.

Study design
19 conditions, each sampled once — no replicated groups

Read from 19 sample titles: 19 distinct titles with little repetition. Check it against the sample list below before relying on it.

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