Zinc Finger Protein 384 (ZNF384) Impact on Childhood Mixed Phenotype
Acute Leukemia and B-Cell Precursor Acute Lymphoblastic Leukemia
Abstract
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a
heterogeneous malignancy and consists of several genetic abnormalities.
Some of these abnormalities are used in clinic for risk calculation and
treatment decision. ZNF384 rearrangements are one of the new oncogenic
subtypes that have been identified in BCP-ALL by recent studies. Also
patients with ZNF384 fusions have been reported in with mixed phenotypic
acute leukemia (MPAL). In this study, we screened 133 pediatric patients
with ALL for the most common ZNF384 fusions; ZNF384-TCF3, ZNF384-EP300
and ZNF384-TAF15 by using qPCR. The total frequency of ZNF384 gene
rearrangements was 8.2% in the cohort. We identified ZNF384 fusions in
9.5% of mixed phenotypic leukemia and 7.6% of BCP-ALL groups.
Moreover, a novel breakpoint was identified in ZNF384-TCF3 fusion.
Patients with MPAL showed significantly higher ZNF384 expression than
BCP-ALL and controls. Patients with ZNF384 rearrangements had
intermediate survival rates based on other subtypes.