{"doi":"10.1038/s41375-021-01346-7","title":"The RNA-binding protein IGF2BP3 is critical for MLL-AF4-mediated leukemogenesis","abstract":"Despite recent advances in therapeutic approaches, patients with MLL-rearranged leukemia still have poor outcomes. Here, we find that the RNA-binding protein IGF2BP3, which is overexpressed in MLL-translocated leukemia, strongly amplifies MLL-Af4-mediated leukemogenesis. Deletion of Igf2bp3 significantly increases the survival of mice with MLL-Af4-driven leukemia and greatly attenuates disease, with a minimal impact on baseline hematopoiesis. At the cellular level, MLL-Af4 leukemia-initiating cells require Igf2bp3 for their function in leukemogenesis. At the molecular level, IGF2BP3 regulates a complex posttranscriptional operon governing leukemia cell survival and proliferation. IGF2BP3-targeted mRNA transcripts include important MLL-Af4-induced genes, such as those in the Hoxa locus, and the Ras signaling pathway. Targeting of transcripts by IGF2BP3 regulates both steady-state mRNA levels and, unexpectedly, pre-mRNA splicing. Together, our findings show that IGF2BP3 represents an attractive therapeutic target in this disease, providing important insights into mechanisms of posttranscriptional regulation in leukemia.","journal":"Leukemia","year":2021,"id":163378,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":289193,"name":"Julia Philipp","orcid":"0000-0001-7236-7379","position":1,"is_corresponding":false},{"id":587447,"name":"Jaspal Bassi","orcid":null,"position":2,"is_corresponding":false},{"id":587448,"name":"Neha Nibber","orcid":null,"position":3,"is_corresponding":false},{"id":587449,"name":"Jolene M. Draper","orcid":null,"position":4,"is_corresponding":false},{"id":586914,"name":"Tasha Lin","orcid":"0000-0003-4281-4152","position":5,"is_corresponding":false},{"id":568807,"name":"Jayanth Kumar Palanichamy","orcid":"0000-0002-3903-7252","position":6,"is_corresponding":false},{"id":683016,"name":"Amit Kumar Jaiswal","orcid":"0000-0002-6566-3580","position":7,"is_corresponding":false},{"id":74084,"name":"Oscar Silva","orcid":"0000-0003-0808-2592","position":8,"is_corresponding":false},{"id":587450,"name":"May Paing","orcid":null,"position":9,"is_corresponding":false},{"id":586916,"name":"Jennifer K. King","orcid":"0000-0002-1001-6044","position":10,"is_corresponding":false},{"id":62176,"name":"Sol Katzman","orcid":"0000-0002-1787-1246","position":11,"is_corresponding":false},{"id":237926,"name":"Jeremy R. Sanford","orcid":"0000-0002-1131-1627","position":12,"is_corresponding":false},{"id":393189,"name":"Dinesh S. Rao","orcid":"0000-0002-0794-9337","position":13,"is_corresponding":false},{"id":586913,"name":"Tiffany Tran","orcid":"0000-0003-2163-3520","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T23:45:22.477398Z","pmid":"34321607","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}