Detection of EP300-ZNF384 fusion in patients with acute lymphoblastic leukemia using RNA fusion gene panel sequencing

Abstract

EP300-ZNF384 fusion is a rare recurrent cytogenetic abnormality associated with B cell acute lymphoblastic leukemia (B-ALL), which was rarely studied in Chinese patient cohort. Here, we used a customized RNA fusion gene panel to investigate gene fusions in 56 selected acute leukemia patients without conventional genetic abnormalities. Two EP300-ZNF384 fusion forms were detected in ten cases, which were in-frame fusions of EP300 exon 6 fused with exon 3 or 2 of ZNF384. The fusions led to the lack of most functional domains of EP300. We firstly reported EP300-ZNF384 fusion in a mixed-phenotype acute leukemia (MPAL) patient whose CD33 and CD13 were negative. The rest nine B-ALL patients with EP300-ZNF384 fusion expressed CD33 and/or CD13. Fifty-six percent of B-ALL patients (5/9) with EP300-ZNF384 fusion were positive with CD10. After the diagnosis of EP300-ZNF384 fusion, 70% of the patients achieved remission after chemotherapy. Our observations indicated that EP300-ZNF384 fusion consists of a distinct subgroup of B-ALL with a characteristic immunophenotype. These patients are sensitive to current chemotherapy regimen and have an excellent outcome.

Keywords: Acute lymphoblastic leukemia; EP300; Fusion; RNA sequencing; ZNF384.

Fig. 1

Structure and sequence of EP300-ZNF384 fusion. a Structural and functional domains of wild-type proteins of EP300 and ZNF384. Arrows indicated breakpoints of the wild-type proteins. b Sanger sequence of the fusion breakpoint between EP300 exon 6 and ZNF384 exon 3. c. EP300-ZNF384 fusion was confirmed by using dual-color FISH probes in interphase nuclei. The green signals were EP300 probes and the red signals were ZNF384 probes. The resulting yellow signal by tandem of red and green signals represented the EP300-ZNF384 fusion