Mixed Phenotype Acute Leukemia, B/Myeloid (Bilineal and Biphenotypic), With t(2;22)(q35;q12);EWSR1-FEV.

Background Ewing sarcoma breakpoint region 1 gene (EWSR1) rearrangements are largely associated with the Ewing sarcoma family of tumors. Observations We report the first case of infantile, mixed phenotype acute leukemia, B/myeloid (bilineal and biphenotypic [B-lymphoid and B-lymphoid/myeloid]), with a t(2;22)(q35;q12). The EWSR1-fifth Ewing variant gene fusion and nonsense mutation in STAG2 were detected by next-generation sequencing and markedly high expression of fifth Ewing sarcoma variant mRNA detected by quantitative reverse transcription polymerase chain reaction. The patient was treated with a combined myeloid/lymphoid leukemia regimen followed by allogeneic stem cell transplant and was in complete remission at 3.8-year follow-up. Conclusions Our case study underscores the importance of a comprehensive evaluation of acute leukemia and provides insights into the phenotype of EWSR1 rearranged neoplasms in the context of partner genes and cell type.