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.

microRNA-200c-3p suppresses proliferation and invasion of nephroblastoma cells by targeting EP300 and inactivating the AKT/FOXO1/p27 pathway

“…Moreover, luciferase activity assay confirmed that miR-200c-3p directly targeted the Western blot showed that the expression of miR-200c-3p was negative correlated with target gene EP300. Previous studies suggested that EP300 may be involved in oncogenic processes in several different carcinomas including lung, prostate, laryngeal squamous cell cancer, breast cancer and leukemia [32][33][34][35][36]. These results suggested that miR-200c-3p played an antitumour role targeting EP300 in nephroblastoma.…”

MRD-Negative Remission Induced in EP300-ZNF384 Positive B-ALL Patients by Tandem CD19/CD22 CAR T-Cell Therapy Bridging to Allogeneic Stem Cell Transplantation

“…3,10,11 However, some patients with EP300-ZNF384 also suffered relapses and were refractory to salvage chemotherapy (Supplementary Table 3). 5 Both patients reported here had weak expression of CD20 and therefore presented no target for anti-CD20 monoclonal antibody or CD20-targeted CAR T-cell therapy. As reported in most cases, exon 6 of EP300 was fused with exon 3 of ZNF384 in both cases.…”

“…6 At present, only two EP300-ZNF384positive B-ALL patients have undergone CAR T-cell therapy; however, both patients died. 5 No details about the efficacy and safety of CAR T-cells for these patients were reported. Despite the high response rate of CD19 CAR T-cell therapy, approximately 50% of R/R B-ALL patients relapsed after CD19 CAR T-cell therapy, which is partially due to CD19 antigen loss.…”

“…Because of its low incidence, there is a shortage of large-sample clinical studies focusing on this entity, and studies on salvage therapy for patients in whom conventional treatments fail are especially rare. 5 Chimeric antigen receptor (CAR) T-cell therapy has shown an encouraging efficacy in refractory and relapsed (R/R) B-ALL. 6 Here, we report the successful application of CAR T-cell therapy using a tandem CD19/CD22 CAR in two R/R B-ALL patients with the EP300-ZNF384 fusion.…”

ZNF384 rearrangement in acute lymphocytic leukemia with renal involvement as the first manifestation is associated with a poor prognosis: a case report

“…It encodes a zinc finger protein that functions as a transcription factor and regulates the expression of matrix metalloproteinases [ 3 ]. In ZNF384 -rearranged BCP-ALL, the breakpoints of ZNF384 are typically located in exons 2 and 3, which contain the entire ZNF384 protein that may be responsible for the characteristics of the immunophenotype [ 4 , 5 ]. Therefore, the presence of ZNF384 rearrangements should be a hallmark and the diagnostic criterion of a separate subtype of BCP-ALL since patients harboring such rearrangements have a distinctive immunophenotype.…”