CEBPA-bZip Mutations Associated With Favorable Prognosis in Acute Myeloid Leukemia

CEBPA basic leucine zipper (CEBPA-bZip) mutations, whether monoallelic or biallelic, are associated with favorable outcomes from acute myeloid leukemia (AML), similar to those with CEBPA-double-mutated (CEBPA-dm), according to research published in Blood.

CEBPA mutations are a common driver for AML and occur in 4% to 11% of patients. This analysis evaluated outcomes data across CEBPA mutation types in 4 different clinical trials.

The analysis included 2958 children and young adults with newly diagnosed AML. A total of 160 patients (5.4%) had CEBPA-bZip mutations; of those 160, 82.5% (132 patients) had a transcription activation domain (TAD) mutation on the other allele and 17.5% (28 patients) had a bZip only mutation. Patients with single TAD mutations were rare (0.15%) and were excluded from the analysis.

Next generation sequencing (NGS) data was available for 1,863 patients. Patients with  CEBPA mutations responded favorably to initial therapy, with a complete remission (CR) rate of 87.7%, compared with 76.9% CR for patients who had CEBPA-wild type (WT) (P =.002).

Patients with CEBPA-dm and CEBPA-bZip mutations each had a 5-year event-free survival (EFS) of 64%. Patients with CEBPA-WT had a 5-year EFS of 46%. Patients with CEBPA-dm and CEBPA-bZip had similar overall survival (OS) of 81% and 89%, respectively.

The study authors also found that patients with CEBPA-bZip only and CEBPA-dm mutations had similar gene expression and transcriptome profiles that were distinctly different than those of patients with CEBPA-WT.

Patients with CEBPA mutations also had enrichment of CSF3R and GATA2 mutations. 13.1% of patients had a co-occurring CSF3R mutation, and 21.5% had a co-occurring GATA2 mutation. The study found that patients with CSF3R mutation and CEBPA mutations had a high relapse rate (83%) and poor EFS (17%).

The World Health Organization (WHO) has classified CEBPA-dm as a distinct entity of myeloid neoplasms and leukemia. It is considered a favorable prognostic feature. The study authors propose that based on these results, patients with bZip mutations, monoallelic or biallelic, be included in WHO guidelines as a prognostic entity.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Tarlock K, Lamble AJ, Wang YC, et al. CEBPA-bZip mutations are associated with favorable prognosis in de novo AML: a report from the Children’s Oncology Group. Blood. 2021;138(13):1137-1147. doi:10.1182/blood.2020009652