Determination of 384 Zinc Finger Protein (ZNF384) gene fusions in acute leukemia patients

Acute leukemia is a group of diseases caused by excessive proliferation of immature blood cells from bone marrow. According to the World Health Organization acute leukemia classification in 2016, acute leukemias are divided into three classes as acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and mixed phenotype acute leukemia (MPAL). ALL consists of B-cell precursor (BCP-ALL), or less commonly, T-cell precursor strain (T-ALL). Both have multiple subtypes, usually defined by structural chromosomal changes. ZNF384 gene rearrangements are one of the new oncogenic subtypes of BCP-ALL. ZNF384 gene rearrangements were reported 1-6% in childhood BCP-ALL, and 5-15% of adult BCP-ALL cases. In addition, cases with ZNF384 rearrangements have an abnormal myeloid marker expression with MPAL. There is limited number of data about the clinical impact of ZNF384 gene rearrangement. Patients carrying ZNF384 fusions are classified into medium risk group need more attention and novel molecular genetic markers are very important for risk adopted treatment strategies. Examinations of different phenotypic ALL subgroups will be help us to understand the clinical impacts of novel markers. The aim of this study was to determine the frequency of the most common ZNF384 fusions in patients with BCP-ALL and MPAL. One hundred twenty-seven pediatric ALL patients (53 females, 74 males) were included in this study. Median age of patients was four. Total RNA was isolated from patients' bone marrow at diagnosis and cDNA synthesis was performed by using random hexameres and MMLV reverse transcriptase. The most common fusions (ZNF384-TCF3, ZNF384-EP300 and ZNF384-TAF15) containing five different breakpoints were examined by using RT-PCR. ZNF384 gene rearrangement was found 7,8% in paediatric ALL patients. We identified ZNF384 fusions 8,3% in mixed phenotypic leukemia and 7,7% in BCP-ALL groups. A novel breakpoint was also identified in ZNF384-TCF3 fusion.