A mini-review published in the Journal of Clinical and Translational Pathology summarizes the clinical and pathological features of acute leukemia cases with FUS or EWSR1 gene rearrangements.
Methods
The authors conducted a literature review of reported acute leukemia cases with FUS or EWSR1 fusions.
Results
- Rare acute leukemias with FUS or EWSR1 rearrangements show heterogeneous clinical and pathological features.
- FUS-rearranged acute leukemias are predominantly acute myeloid leukemia (AML), with ERG as the most common fusion partner, and display diverse immunophenotypes.
- EWSR1-rearranged acute leukemias more often present as B-cell acute lymphoblastic leukemia (ALL) or mixed phenotypic acute leukemia (MPAL), with ZNF384 as the predominant partner.
- FUS::ERG-positive AML is the only entity with a FET::ETS fusion formally recognized in WHO-HEM5 and ICC classifications.
- Cytogenetic karyotyping and fluorescence in situ hybridization detect chromosomal translocations in over half of these leukemias, but some patients have a normal karyotype and require advanced molecular diagnostics.
- Distinguishing EWSR1-rearranged leukemia from Ewing sarcoma requires additional workup, including immunohistochemical staining.
Conclusions
- The authors suggest that the category of acute leukemias with FET::ETS fusions could be expanded to include FUS::FLI1 and FUS::FEV, pending more data.
- EWSR1-rearranged AML cases are very rare and heterogeneous.
- B-ALL or B/myeloid MPAL with EWSR1::ZNF384 may be better classified under ZNF384-rearranged leukemia subtypes.
- RNA-based next-generation sequencing is recommended for accurate diagnosis.