Abstract
Transducin-like enhancer of split 1 (TLE1) is a member of the TLE family of transcriptional co-repressors that control the transcription of a wide range of genes. The aim of this study was to evaluate the prognostic role of TLE1 gene expression in patients with T-cell acute lymphoblastic leukemia (T-ALL).
This study was conducted on 97 newly diagnosed T-ALL patients admitted to the Mansoura University Oncology Center (59 males and 38 females), with a median age of 33 years, in addition to 102 apparently healthy individuals who served as a control group. TLE1 gene expression was measured in both the patient and control groups by real-time PCR. The calculation of relative gene expression was done using the δδCt: method.
TEL1 gene expression was significantly downregulated in T-ALL cases (median 2.83) compared to controls (median 84.65; P<0.001). Low TEL1 gene expression was significantly associated with CNS infiltration, failure to achieve the first complete remission, and a higher relapse rate (P<0.001, 0.001, and 0.023, respectively). The early T-cell precursor (ETP)-ALL/LBL subtype was found to be significantly associated with low TEL1 gene expression (P=0.04); however, no relations between TEL1 gene expression and TCR rearrangement or other known molecular abnormalities were found. Likewise, low TEL1 gene expression was significantly associated with shorter OS and DFS (P=0.012 and 0.011, respectively). Furthermore, low TEL1 gene expression was considered a risk predictor of relapse, with OR 3.636 (CI: 1.422–9.295; P=0.007) in univariate analysis and OR 0.803 (CI: 0.609–0.96; P=0.021) in multivariate analysis, and an independent predictor of T-ALL patient outcomes, with OR 0.619 (CI:0 .44–0.872; P=0.006).
TLE1 gene expression was significantly downregulated in T-ALL compared with controls. Low TLE1 expression is an independent predictor of T-ALL patient outcomes and could open avenues for further risk stratification and targeted therapy in T-ALL.