Aggressive Disease and Poor Clinical Outcome in CEBPα-Mutated Acute Myeloid Leukemia Patient

CCAAT/enhancer binding protein α (C/EBPα) mutations occur in about 4%-11% of AML patients and are typically associated with favorable prognosis. Here we present a case of AML with two distinct CEBPα variants exhibiting an unexpectedly poor clinical outcome despite intensive chemotherapy and molecular remission at an early phase of treatment. Routine diagnostic work-up included in-house morphological assessment, flow cytometry, molecular and cytogenetics testing, and NGS-based CNV testing. A 63-year-old male with a history of trigeminal neuralgia presented to the ER with fever associated with sore throat, cough and spontaneous bruising accompanied by leucocytosis (WBC, 52.4 × 10⁹/L) and thrombocytopenia (PLT, 26 × 10³/μL). Bone marrow evaluation revealed 95% blasts consistent with acute leukemia with flow cytometry confirming the diagnosis. Myeloid NGS panel revealed two distinct likely pathogenic CEBPα variants: c.315del; p. F106Lfs*54 in TAD2 and c.941_946dupTGCTGG; p.V314_L315dup in the bZip domain. The patient received 7 + 3 induction chemotherapy followed by HiDAC consolidation when he achieved remission. He subsequently relapsed with progressive disease accompanied by multiple complications and persistent MRD-positivity despite multiple salvage regimens and SCT. CEBPα-mutated AML presents a complex challenge to conventional chemotherapy and may require alternative treatment strategies including transplantation. Additionally, genomics technologies in AML have the potential to uncover known and novel gene variants.