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Lymphoid enhancer binding factor 1 is an important member of the LEF/ T cell factor transcription factors family. It has an important role in cellular proliferation and cell cycle regulation. It is traditionally regarded as a central mediator of the Wnt/ β catenin signaling pathway. It has vital function in early hematopoiesis and leukemic transformation in murine models.
Wnt signaling pathway has diverse and fundamental functions in physiological (such as embryogenesis, organogenesis, proliferation, tissue repair and cellular differentiation) and pathological (carcinogenesis, congenital/genetic diseases, and tissue degeneration) processes. Wnt signaling pathway aberrations are associated with both solid tumors and hematological malignancies.
The aim of the present study was to evaluate LEF1 mRNA expression levels in adult patients with AML and correlate this expression with clinical, immunophenotypic, cytogenetic data and other prognostic factors to detect the effect of LEF1 expression on patients’ outcome.
The study was performed on 30 newly diagnosed AML patients attending the Hematology Oncology unit of Ain Shams University Hospital and 10 healthy volunteers matching in age and sex during the period from May 2017 till May 2018.
Our results showed that LEF1 expression is significantly upregulated in AML patients (6.72 ± 5.40 log10) and may serve as a novel predictor of better treatment response as high LEF1 expression is associated with a favorable outcome and better overall survival.
There was a significant positive correlation between LEF1 expression level and Hb level, PLT count, OS and DFS. While a significant negative correlation was found with age, TLC count and PB blast %. No correlation was found with BM blasts %.
There was highly statistically significant association between LEF1 expression level and both FAB and cytogenetic classifications where high LEF1 expression level was associated with favorable FAB classification (M2, M3, M4) and good cytogenetic prognosis group.
High LEF1 expression patients were associated with favorable treatment outcomes as they had better OS than patients with low LEF1 expression levels with mean of 6.40 ± 2.59 months versus 2.0 ± 2.59 months with statistically significant difference.
There was a highly statistically significant differences between low and high LEF1 expression patients as regard response to therapy where the majority of patients with high LEF1 expression achieved hematological remission while all patients with low LEF1 expression did not achieve hematological remission, they either achieved incomplete remission or died.
A cut-off value for evaluating the prognostic performance of LEF1 expression was established according to ROC curve analysis. A cut off value of ≤10.11 log10 was found to have a sensitivity of 90.48% and specificity of 100% in discriminating between hematological remitted patients from non remitted or dead.
Logistic regression analysis was performed to determine the prognostic significance of LEF1 expression after adjusting for the impact of other standard risk factors (age and cytogenetics). In univariant model for hematological remission achievement, LEF1 expression patients showed an odds ratio of 2.29 fold increase toward achieving hematological remission (P=0.049 and 95% confidence interval was 1.001-5.27).