Clinical characteristics and outcomes of B-ALL with ZNF384 rearrangements: a retrospective analysis by the Ponte di Legno Childhood ALL Working Group
Abstrakt
ZNF384 fusions are an enigmatic group of gene fusions which span the ALL-MPAL disease spectrum and are not readily detected and characterized by traditional genetic testing.It is definitey required to screen by FISH, reverse transcription polymerase chain reaction or RNA sequencing. The major strengthen of this study is that it has collated a large well-annoatated cohort of ZNF384-fusion patients which while not uninformly treated were all diagnosed with ALL and treated as such.
As with all retrospective consortia-based studies the limitations are heterogeneity in terms of recrtuiment period and treatment decisions and pathways. Nonetheless, we provide good evidence that among B-ALL patients with a ZNF384 fusion the partner gene is associated with demographic features and influences outcome, specifically with EP300-ZNF384 being associated with a lower risk of relapse.
We opted to exlude MPAL cases because, historically, they have not been treated uniformly. A recent international cooperative study has defined a consensus treatment staregy for MPAL patients.
This initiative coupled with improved diagnostic genomic testing will enable future prospective studies to clarify the clinical relevance of the fusions in both ALL and MPAL.