{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306536/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306536"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Effect on gene expression and RNA splicing with CRISPR/Cas9 knockout of PTBP1, PTBP2, or both in MOLM-13, MV4-11, and K-562 human leukemia cell lines","description":"RNA-modifying enzymes (RNAes) and RNA-binding proteins (RBPs) have emerged as critical gene regulators in both normal physiology and cancer. To systematically evaluate their necessity in cancer, we performed domain-focused CRISPR screens targeting RNAes and RBPs across a broad spectrum of cancer cell lines. These screens identified novel acute myeloid leukemia (AML) dependencies, including PTBP1, with a bias toward KMT2A-rearranged (KMT2A-r) AML, an aggressive subtype with poor clinical outcomes. Genetic and cellular validation confirmed all four RNA-binding domains in PTBP1 are required for KMT2A-r AML proliferation. PTBP1 loss led to cell cycle arrest, apoptosis, and induction of myeloid differentiation programs. Transcriptomic analyses revealed widespread dysregulation of gene expression and splicing. eCLIP-seq further showed PTBP1 binds to a subset of these transcripts critical for AML proliferation, including ACSL4, DPF2, and IKZF1. Our findings demonstrate that PTBP1 supports AML proliferation by fine-tuning the expression and splicing of AML-essential genes and provide a workflow for systematically annotating RNAe and RBP dependencies in cancer.","dates":{"publication":"2026/08/10"},"accession":"GSE306536","cross_references":{"GSM":["GSM9202897","GSM9202898","GSM9202895","GSM9202896","GSM9202912","GSM9202910","GSM9202899","GSM9202911","GSM9202890","GSM9202893","GSM9202894","GSM9202891","GSM9202892","GSM9202905","GSM9202906","GSM9202903","GSM9202904","GSM9202909","GSM9202907","GSM9202908","GSM9202886","GSM9202887","GSM9202885","GSM9202901","GSM9202902","GSM9202888","GSM9202900","GSM9202889"],"GPL":["24676","34284"],"GSE":["306536"],"taxon":["Homo sapiens"]}}