SET (TAF-IB) Gene Is Highly Expressed in Acute Leukemia Patients without Associated with Methylation Status.
Authors: Sirma Sema , Ekmekçi Cumhur G. , Kandilci Ayten , Grosveld Gerard , Ozbek Ugur 
Published: April 2020

SET gene, also known as TAF-I beta, was originally identified as a component of the SET-CAN fusion gene, which results from t(9;9) translocation, in a patient with acute undifferentiated leukemia (AUL). SET gene encodes a nuclear phosphoprotein that ubiquitously expressed. There is an accumulating data that suggest a role for SET in gene silencing either through prevention of histone acetylation as a subunit of inhibitor of acetyltransferases (INHAT) complex or through inhibition of DNA demethylation. SET also inhibits the activity of protein phosphatase 2A, which involves in regulation of cell proliferation and differentiation, and blocks DNase activity of the tumor metastasis suppressor NM23-H1. Taken together, available data suggest that SET might play a role in tumorogenesis via tumor suppressor gene silencing or inhibition of apoptosis.

In this study, we investigated SET gene expression level in bone marrow samples of 77 patients with acute leukemia (57 acute lymphoblastic leukemia (ALL) and 26 acute myeloid leukemia (AML)) and 5 control bone marrow samples from healthy volunteers using quantitative real-time RT-PCR. The ALL patient ages ranged 10months – 17 years, with a median of 6 years and the AML patient ages ranged 1–72 years, with a median of 18 years. For determination of the prognostic significance of SET gene expression in ALL patients, the association between patient’s clinical characteristics and the SET gene expression level was assessed usind the Pearson’s chi-square test or Fisher’s Exact test. Overall survival (OS) in 48 patients and relapse-free survival (RFS) in 37 patients with ALL at 6 years (median follow-up 35 months, range 1–79 months) were analyzed according to Kaplan-Meier method. We also studied methylation of various genes (p15, p16, p73, SOCS1, RAR beta, E-Cadherin, GSTP1, DAP-Kinaz, ER and 5-HIC) using methylation spesific PCR and COBRA analysis in AML samples to examine whether high SET gene expression play a role in tumorogenesis via gene silencing.

Here we demonstrate that 54.4% of ALL patients and 53.8% of AML patients show two fold and higher SET expression level compare to control samples (p=0.005 and p=0.016 respectively). There were no significant association between SET gene expression level and age, peripheral WBC count, sex, FAB group and immunophenotype (P=0.823, P=0.182, P=1.00, P=0.132, P=0.751) in ALL. The OS was not significantly different between high (83.10% ± 6.92%) and low SET expressed patients (51.14% ± 18.73%) (log-rank=3.36, P=0.067) and the probability of RFS was not significantly different between high (81.20% ± 7.60%) and low SET expressed patients (80.00% ± 17.89%) with ALL (log-rank=0.01, P= 0.92). There was no statisticall association between methylation index and SET gene expression level (P=0.618).

Our data suggest that high level of SET expression may play an important role in leukemogenesis. Further analyses are required to determine prognostic significance of SET gene expression different types of leukemia.