Introduction

Germline CEBPA-mutant acute myeloid leukaemia (AML) is uncommon. There have been reports of single kindreds and small series1–6 since its initial description in 2004;7 and the most comprehensive characterisation comprising 10 CEBPA-mutant families was recently published.8 We herein describe another patient with AML with a germline CEBPA mutation encountered in our haematology practice.

The patient was a 33-year-old Vietnamese man who presented with a 2-week history of easy bruising and generalised fatigue. Initial investigations revealed haemoglobin of 11.6 g/dL, white cell count of 3.98×10⁹/L and platelet count of 35×10⁹/L. His marrow was moderately hypercellular with increased pleomorphic blasts, consistent with AML subtype M2 (figure 1). Of note, occasional pelgeroid neutrophils were observed. Flow cytometry was performed using a panel of markers, which included CD7, CD15, CD34, CD36, CD45, CD56, CD71, CD117 and HLA-DR. This revealed the presence of CD34-positive myeloblasts (comprising 5.8% of total cells), as well as dys-coordinated granulopoiesis (with partial CD56 expression) and markedly dysplastic erythropoiesis (with partial CD36/CD71 expression), overall suggestive of clonal evolution from a myelodysplastic syndrome (MDS). Cytogenetic analysis revealed a 46,XY,del(9)(q13q22) karyotype. CEBPA mutational analysis by Sanger sequencing revealed two mutations: c.134dupC and c.937_938ins33 (figure 2).

He was started on induction chemotherapy, and flow cytometric analysis of the bone marrow postinduction revealed 0.8% minimal residual disease (MRD). Unexpectedly, CEBPA mutational analysis revealed persistence of the c.134dupC mutation, raising the suspicion of a germline CEBPA mutation. This was subsequently confirmed by CEBPA mutational …