EWSR1-and FUS-rearranged acute leukemias: Clinicopathological and genomic characterization.

BACKGROUND

EWSR1::FEV and FUS::FEV fusions, belonging to the FET-ETS family gene fusions, are extremely rare in acute leukemias. Our study aims to characterize the clinicopathologic and genomic profiles of this rare entity.

METHODS

Clinical, morphologic, immunophenotypic, cytogenetic, and genomic features were analyzed in three patients with leukemia harboring these rare fusions.

RESULTS

These leukemias were characterized by a female predominance with variable age of onset (a median age of 27 years), heterogenous leukemia phenotypes [acute myeloid leukemia/AML with EWSR1::FEV (n = 1) and mixed phenotype acute leukemia/MPAL (n = 2) with B/myeloid (EWSR1::FEV) and T/myeloid (FUS::FEV) phenotype], additional cytogenetic abnormalities (3/3) in addition to cryptic (2) or non-cryptic (1) fusion related chromosomal translocations, and co-occurring gene mutations in signaling pathway (PTPN11, 2/3) and cohesin complex (STAG2, 1/3). The prognosis of EWSR1::FEV and FUS::FEV leukemias is largely unknown; all three patients were alive with a median follow-up of 46 months, but one patient relapsed.

CONCLUSION

This is the first case series study, including the first case description of FUS::FEV leukemia, to characterize clinicopathologic and genomic features of leukemias with EWSR1::FEV and FUS::FEV and provide insights into the leukemogenesis of this rare entity. Furthermore, we recommend inclusion of FET-ETS fusions in future acute leukemia classification schemes.