Hypoplastic acute myeloid leukemia with aberrant lymphoid antigen expression and EWSR1::FEV fusion: A rare case report and literature review.

Abstract

Ewing sarcoma breakpoint region 1 (EWSR1):: Fifth Ewing variant (FEV)-positive acute leukemia is exceptionally rare, and its clinicopathological features, molecular profile, and optimal treatment remain poorly defined. Here, we report a case of acute myeloid leukemia (AML) with bone marrow hypocellularity, aberrant lymphoid antigen expression, and an EWSR1::FEV fusion. A 45-year-old man was admitted with a 1-month history of petechiae and fatigue. Complete blood count (CBC) showed pancytopenia. Bone marrow (BM) examination revealed hypocellular marrow, with blasts accounting for 62% of nucleated cells. Flow cytometry (FCM) revealed a predominantly myeloid immunophenotype accompanied by aberrant expression of lymphoid-associated antigens. Conventional karyotyping did not identify a characteristic balanced translocation. Targeted next-generation sequencing (NGS) detected concurrent PTPN11 and NRAS mutations. RNA sequencing (RNA-seq) of the bone marrow sample identified the EWSR1::FEV fusion. Based on these findings, the patient was diagnosed with de novo AML with bone marrow hypocellularity and aberrant lymphoid antigen expression. Given the hypocellular marrow, venetoclax plus azacitidine (VA) was selected as induction therapy. The patient achieved morphological complete remission after one cycle, accompanied by a marked reduction in EWSR1::FEV transcript levels, and remained in morphological remission during approximately 6 months of follow-up after subsequent homoharringtonine combined with venetoclax plus azacitidine (HVA) consolidation. Together with previously reported cases, this case further supports the notion that EWSR1::FEV-positive acute leukemia may represent a distinct molecular subset characterized by lineage ambiguity, fusion-driven biology, and potentially unique therapeutic vulnerabilities. This case also suggests potential activity of venetoclax-based therapy in EWSR1::FEV-positive leukemia and warrants further investigation in additional cases.