GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE263nnn/GSE263684/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE263684GEOGSEfalseMBNL1 hijacks a structured single-stranded distal DNA element to sustain FLT3 expression in KMT2A-rearranged leukemiasThe 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.2026/06/10GSE263684GSM9145579GSM8196554GSM9145578GSM8196553GSM9145577GSM9145576GSM8196551GSM9145575GSM8196550GSM9145574GSM9648430GSM9145573GSM9145572GSM9145580GSM9648429GSM9648431GSM9648432GSM8196549GSM819654824676263684Homo sapiens