The prognosis for patients diagnosed with acute myeloid leukemia (AML) suitable for intensive chemotherapy, is defined by the presence of specific genetic abnormalities.1,2 Among these, mutations in CCAAT/enhancer binding protein a (CEBPA) gene have classically classified as favorable risk.3 The frequency of CEBPA gene mutations ranges from 7% to 20%,4,5 being present mostly in cytogenetically normal patients. While wild-type CEBPA (CEBPAwt) or CEBPA single-mutation (CEBPAsm) patients have ~60% risk of relapse, this risk is ~40% in those with CEBPA double mutation (CEBPAdm).5 These findings led to the inclusion of CEBPAdm AML as a distinct diagnostic entity in the 2016 World health Organization (WHO) classification6 and as favorable risk group by 2017 European Leukemia Net (ELN) risk classification.7 However, a study in children and young adults enrolled in Children’s Oncology Group trials showed that CEBPA mutations in bZIP region conferred favorable prognosis, regardless of whether they are CEBPAsm or CEPBAdm.8 This finding was confirmed in adult patients enrolled in protocols of the Study Alliance Leukemia,9 where bZIP mutations were associated with higher overall survival (OS) and complete remission (CR) rate. This data led to refinement of 2022 ELN risk classification,2 defining as favorable risk only the presence of inframe bZIP CEBPA mutation (CEBPA-bZIP-inf).

This investigation was partially supported by Instituto de Salud Carlos III, Spain, grant PMP22/00069 and PI19/00730.

Peer reviewed