{"doi":"10.1172/jci142627","title":"Doubling up on function: dual-specificity tyrosine-regulated kinase 1A (DYRK1A) in B cell acute lymphoblastic leukemia","abstract":"Kinases comprise a large class of eukaryotic proteins that evolved to regulate key cellular processes by chemically adding phosphates to modulate protein function. DYRK1A (dual-specificity tyrosine-regulated kinase 1A) is among a conserved family of CMGC kinases (named by the first letter of the family members, including cyclin-dependent kinases, mitogen-activated protein kinases, glycogen synthase kinase 3, and, CDK-like kinases) (1). On the basis of structure and function, DYRK kinases are designated class I (DYRK1A, DYRK1B) or class II (DYRK2, DYRK3, DYRK4). DYRK1A is considered to have dual specificity because it phosphorylates diverse regulatory proteins at serine/threonine residues and autophosphorylates its own activation loop to enhance its activity (1). DYRK1A has been intensely investigated, given its positioning on the Down syndrome (DS) critical region of chromosome 21 (HSA21) (1, 2), and was later linked to autism and Alzheimer's disease (1, 3-5). Mice that have heterozygous Dyrk1a deficiency recapitulate many of the neurodevelopmental phenotypes observed in DS (1). DS is also associated with a predisposition to cancer, including B cell acute lymphoblastic leukemia (B-ALL), although the mechanisms underlying these seemingly disparate pathologies have remained elusive until now (2, 6). As reported in this issue of the JCI, Bhansali, Rammohan, and coauthors' work on DYRK1A sheds light on why individuals with DS develop B-ALL (2). This study also reveals signaling pathways that occur not only in B-ALL in DS, but also in B-ALL with HSA21 polyploidy. Thus, in addition to dual specificity, DYR-K1A function, ironically, has dual roles in B-ALL. Notably, the DYRK1A signaling pathway also provides a promising therapeutic target.","journal":"Journal of Clinical Investigation","year":2021,"id":200779,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9605,"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":336882,"name":"Liping Li","orcid":"0000-0002-6884-6059","position":1,"is_corresponding":false},{"id":311494,"name":"Linda Resar","orcid":"0000-0002-4004-7060","position":2,"is_corresponding":false},{"id":445948,"name":"Jung‐Hyun Kim","orcid":"0000-0001-7176-409X","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-18T23:50:48.624274Z","pmid":"33393492","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":[]}