{"doi":"10.1158/0008-5472.c.6500330","title":"Data from Altered Runx1 Subnuclear Targeting Enhances Myeloid Cell Proliferation and Blocks Differentiation by Activating a miR-24/MKP-7/MAPK Network","abstract":"<div>Abstract<p>Disruption of Runx1/AML1 subnuclear localization, either by a single amino acid substitution or by a chromosomal translocation [e.g., t(8;21)], is linked to the etiology of acute myeloid leukemia (AML). Here, we show that this defect induces a select set of micro-RNAs (miR) in myeloid progenitor cells and AML patients with t(8;21). Both Runx1 and the t(8;21)-encoded AML1-ETO occupy the miR-24-23-27 locus and reciprocally control miR-24 transcription. miR-24 directly downregulates mitogen-activated protein kinase (MAPK) phosphatase-7 and enhances phosphorylation of both c-<i>jun</i>-NH<sub>2</sub>-kinase and p38 kinases. Expression of miR-24 stimulates myeloid cell growth, renders proliferation independent of interleukin-3, and blocks granulocytic differentiation. Thus, compromised Runx1 function induces a miR-dependent mechanism that, through MAPK signaling, enhances myeloid proliferation but blocks differentiation—key steps that contribute to leukemia. [Cancer Res 2009;69(21):8249–55]</p></div>","journal":null,"year":2023,"id":404949,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1183667,"name":"Christopher R. Dowdy","orcid":null,"position":1,"is_corresponding":false},{"id":275536,"name":"André J. van Wijnen","orcid":"0000-0002-4458-0946","position":2,"is_corresponding":false},{"id":288843,"name":"Jane B. Lian","orcid":"0000-0001-8683-9138","position":3,"is_corresponding":false},{"id":558771,"name":"Azra Raza","orcid":"0000-0002-9734-5210","position":4,"is_corresponding":false},{"id":147373,"name":"Janet L. Stein","orcid":null,"position":5,"is_corresponding":false},{"id":247626,"name":"Carlo M. Croce","orcid":"0000-0003-3788-1457","position":6,"is_corresponding":false},{"id":49920,"name":"Gary S. Stein","orcid":"0000-0001-8762-5422","position":7,"is_corresponding":false},{"id":373282,"name":"Sayyed K. Zaidi","orcid":"0000-0001-6664-5168","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T01:20:49.237119Z","pmid":null,"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":[]}