{"doi":"10.1182/blood.2020009652","title":"<i>CEBPA</i>-bZip mutations are associated with favorable prognosis in de novo AML: a report from the Children’s Oncology Group","abstract":"Biallelic CEBPA mutations are associated with favorable outcomes in acute myeloid leukemia (AML). We evaluated the clinical and biologic implications of CEBPA-basic leucine zipper (CEBPA-bZip) mutations in children and young adults with newly diagnosed AML. CEBPA-bZip mutation status was determined in 2958 patients with AML enrolled on Children's Oncology Group trials (NCT00003790, NCT0007174, NCT00372593, NCT01379181). Next-generation sequencing (NGS) was performed in 1863 patients (107 with CEBPA mutations) to characterize the co-occurring mutations. CEBPA mutational status was correlated with disease characteristics and clinical outcomes. CEBPA-bZip mutations were identified in 160 (5.4%) of 2958 patients, with 132 (82.5%) harboring a second CEBPA mutation (CEBPA-double-mutated [CEBPA-dm]) and 28 (17.5%) had a single CEBPA-bZip only mutation. The clinical and laboratory features of the 2 CEBPA cohorts were very similar. Patients with CEBPA-dm and CEBPA-bZip experienced identical event-free survival (EFS) of 64% and similar overall survival (OS) of 81% and 89%, respectively (P = .259); this compared favorably to EFS of 46% and OS of 61% in patients with CEBPA-wild-type (CEBPA-WT) (both P < .001). Transcriptome analysis demonstrated similar expression profiles for patients with CEBPA-bZip and CEBPA-dm. Comprehensive NGS of patients with CEBPA mutations identified co-occurring CSF3R mutations in 13.1% of patients and GATA2 mutations in 21.5% of patients. Patients with dual CEBPA and CSF3R mutations had an EFS of 17% vs 63% for patients with CEBPA-mutant or CSF3R-WT (P < .001) with a corresponding relapse rate (RR) of 83% vs 22%, respectively (P < .001); GATA2 co-occurrence did not have an impact on outcome. CEBPA-bZip domain mutations are associated with favorable clinical outcomes, regardless of monoallelic or biallelic status. Co-occurring CSF3R and CEBPA mutations are associated with a high RR that nullifies the favorable prognostic impact of CEBPA mutations.","journal":"Blood","year":2021,"id":148640,"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":122,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"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":278806,"name":"Adam J. Lamble","orcid":"0000-0002-7781-2918","position":1,"is_corresponding":false},{"id":632411,"name":"Yi‐Cheng Wang","orcid":"0000-0003-2432-5128","position":2,"is_corresponding":false},{"id":418961,"name":"Robert B. Gerbing","orcid":null,"position":3,"is_corresponding":false},{"id":632412,"name":"Rhonda E. Ries","orcid":"0000-0002-3702-7923","position":4,"is_corresponding":false},{"id":515041,"name":"Michael R. Loken","orcid":"0000-0002-0335-9065","position":5,"is_corresponding":false},{"id":632413,"name":"Lisa Eidenschink Brodersen","orcid":"0000-0002-6747-4695","position":6,"is_corresponding":false},{"id":515673,"name":"Laura Pardo","orcid":null,"position":7,"is_corresponding":false},{"id":417604,"name":"Amanda R. Leonti","orcid":"0000-0002-2121-1873","position":8,"is_corresponding":false},{"id":632414,"name":"Jenny L. Smith","orcid":"0000-0003-0402-2779","position":9,"is_corresponding":false},{"id":633541,"name":"Tiffany A. Hylkema","orcid":null,"position":10,"is_corresponding":false},{"id":632415,"name":"William G. Woods","orcid":"0000-0002-5412-2084","position":11,"is_corresponding":false},{"id":603208,"name":"Todd M. Cooper","orcid":"0000-0002-1203-2371","position":12,"is_corresponding":false},{"id":417605,"name":"E. Anders Kolb","orcid":"0000-0003-2854-9014","position":13,"is_corresponding":false},{"id":263217,"name":"Alan S. Gamis","orcid":"0000-0003-1513-2893","position":14,"is_corresponding":false},{"id":85409,"name":"Richard Aplenc","orcid":"0000-0001-7482-5644","position":15,"is_corresponding":false},{"id":85412,"name":"Todd A. Alonzo","orcid":"0000-0002-6772-6581","position":16,"is_corresponding":false},{"id":417606,"name":"Soheil Meshinchi","orcid":"0000-0002-6276-4423","position":17,"is_corresponding":false},{"id":632410,"name":"Katherine Tarlock","orcid":"0000-0001-9717-2973","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:42:46.224799Z","pmid":"33951732","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":[]}