Adverse outcomes and high incidence of therapy-related neoplasms in patients with the t(16;21)/ RUNX1 :: RUNX1T3 fusion

The t(16;21)(q24;q22) translocation creates the RUNX1::RUNX1T3 (also known as CBFA2T3, MTG16) fusion gene, representing a rare but clinically significant subtype of myeloid neoplasms. This comprehensive study presents detailed clinical, immunophenotypic, cytogenetic, and molecular data from 10 new cases while integrating findings from 35 previously reported cases. Patients showed a median age of 48 years with notable female predominance. Immunophenotypic analysis consistently demonstrated a distinctive hybrid myeloid/B-lymphoid phenotype characterized by CD19 co-expression with myeloid markers. Cytogenetic evaluation revealed additional chromosomal abnormalities in 75.6% of cases, with trisomy 8 being most frequent (42.2%). Next-generation sequencing identified recurrent mutations in ASXL1 (50%), TET2, JAK2, and NRAS (each 25%). Clinically, this fusion strongly correlated with therapy-related myeloid neoplasms and demonstrated significantly worse survival outcomes compared to RUNX1::RUNX1T1 AML, highlighting its distinct clinicopathological features and adverse prognostic implications.