Location matters: topography of germline CEBPA variants in familial acute myeloid leukaemia.

Germline CEBPA variants (TAD2 vs non-TAD2 domain) → distinct AML phenotype: age at onset, cooperating somatic variant burden, remission rates

56 patients with familial AML harboring germline CEBPA variants from 40 families (including one new pedigree with a novel TAD2 variant p.C133Ter) were analyzed. TAD2 domain variant localization was associated with later onset (40 vs 21 years, p<0.001), higher cooperating somatic variant burden (64.3% vs 27.3%), and lower complete remission rates. This genotype-phenotype correlation is directly applicable to genetic counseling and surveillance of asymptomatic carriers.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Familial CEBPA AML is often under-recognized due to unclear diagnostic criteria. This integrated 40-family cohort demonstrates that variant topography (TAD2 vs non-TAD2) carries real prognostic value — a message immediately applicable in oncogenetics consultations to stratify hematological surveillance of carriers.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 2/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 8/10