Lymphoid enhancer-binding factor 1 (LEF-1): a favorable prognostic factor in adult acute myeloid leukemia in Egyptian patients

Botheina Ahmed Thabet Farweez,Shaimaa Abdelmalik Pessar,Nahela Ahmed Shalaby,Raghda El Sayed Abdel Monem Galal,Nashwa El-Khazragy,Doaa Ahmed Gamal Eissa

doi:10.1186/s43042-020-00073-5

Abstract

BackgroundCanonical wingless-type (Wnt) signaling is a crucial pathway involved in normal hematopoiesis and the self-renewal process of hematopoietic stem cells. Deregulation of this pathway has been associated with different subtypes of leukemia. Lymphoid enhancer-binding factor 1 (LEF-1) is a major transcription factor of this pathway and plays a pivotal role in lymphoid differentiation and granulopoiesis. High LEF-1 expression has been reported as a prognostic marker in several types of adult hematological malignancies. We aimed to assess the prognostic utility of LEF-1 expression in adult de novo acute myeloid leukemia (AML) Egyptian patients in continuation of our previous work. LEF-1 expression was analyzed by real-time polymerase chain reaction (PCR) in 30 adults with newly diagnosed AML and remeasured at day 28 after induction therapy with the assessment of remission status.ResultsPatients were classified according to median expression level into high and low LEF-1 expression groups. LEF-1 levels were dramatically decreased following successful induction therapy. Also, high LEF-1 expression patients had a better response to therapy with better overall survival. ROC curve analysis of LEF-1 expression yielded a cutoff value of < 10.11 log10 (sensitivity of 90.48% and specificity of 100%) for predicting poor outcome. Univariate logistic regression analysis showed that for every log10 increase in the LEF-1 expression level, the chance of the patient to achieve hematological remission was increased by 2.29 folds.ConclusionOur study showed preliminary results that overexpression of LEF-1 is a favorable prognostic factor in newly diagnosed adult AML patients. The prognostic value of LEF-1 could suggest its utility for further risk classifications of AML and potentiality for being a target for therapy.

Highlights

Canonical wingless-type (Wnt) signaling is a crucial pathway involved in normal hematopoiesis and the self-renewal process of hematopoietic stem cells
Univariate logistic regression analysis was performed to determine the prognostic significance of Lymphoid enhancer-binding factor 1 (LEF-1) expression after adjusting for the impact of other standard risk factors showed that the chance of the patient to achieve hematological remission was increased by 2.29 folds with every log10 increase in the LEF-1 expression level (Table 4)
Searching for new molecular prognostic markers, we studied the relevance of Lymphoid enhancer-binding factor 1 (LEF1) expression in acute myeloid leukemia (AML)

Summary

Introduction

Canonical wingless-type (Wnt) signaling is a crucial pathway involved in normal hematopoiesis and the self-renewal process of hematopoietic stem cells. Deregulation of this pathway has been associated with different subtypes of leukemia. Lymphoid enhancer-binding factor 1 (LEF-1) is a major transcription factor of this pathway and plays a pivotal role in lymphoid differentiation and granulopoiesis. Lymphoid enhancer-binding factor 1 (LEF-1) is a transcription factor of the Wingless-type (Wnt)/β catenin signaling pathway which controls the proliferation, survival, and differentiation of hematopoietic cells through its effect on target genes like c-myc, cyclin D1 [1]. In healthy cells, secreted and/or intracellular located inhibitory proteins tightly control β catenin levels [4]

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