Abstract
Background Deregulation of the Wnt signaling pathway had a role in haematological malignancies. Previous studies reported that lymphoid enhancer factor 1 (LEF1) expression and serum Galectin-3 level could affect clinical parameters and outcome in acute myeloid leukemia patients, but as far as we know, no study has addressed their combined effect on AML patients. Aim We studied the expression of LEF1 by real-time qPCR and measured serum level of Gal.3 by ELISA technique in peripheral blood of 69 AML patients and correlated it with different clinicopathological criteria of patients, response, PFS and OS. Results We found high expression (LEF1high) was associated with better OS (p = 0.02) and EFS (p = 0.019) compared to LEF1low, low serum Gal.3 level had better OS (p = 0.014) and EFS (p = 0.02) compared to high serum Gal.3 level. LEF1high less likely to carry a FLT3-ITD (p = 0.047) compared to LEF1low patient, also LEF1high characterized by favorable risk (p = 0.02) than LEF1low patients. While patients with higher Gal-3 levels characterized by poor risk (p = 0.02) than lower Gal.3 lels, also more likely to carry a FLT3-ITD with borderline significance (p = 0.054). Combined LEF1high/Gal.3 low patients had lower baseline blast percentages (p = 0.02), favorable risk (p = 0.01), less likely to carry FLT3-ITD (p = 0.02), higher CR rate (p = 0.055), shorter time to CR (0.001) than other groups. Among high Gal.3 level group, LEF1highexpression improved OS and EFS (20 and 15 months respectively) vs LEF1low expression (13 and 8 months respectively). Conclusion We conclude that high LEF1 expression was a favorable prognostic marker which can define AML patient risk and outcome independent from assessing the serum galectin.3 level.
Highlights
E function of β catenin is under control of Wnt pathway, in case of absence of Wnt ligand, β catenin will be primed for degradation by proteasomes through its phosphorylation by destruction complex (GSK3β, CK1, Axin and APC), on the other hand when Wnt ligand binds its receptor (Frizzled and LRP5/6) the level of indestructible phosphorylated β catenin will increase saturation of the dendritic cells (DC) leading to cytosolic accumulation of nonphosphorylated β-catenin which translocate to the nucleus forming complexes with the T-cell factor (TCF)/lymphoid enhancer factor (LEF) transcriptional regulators and promotes activation of proto-oncogenic Wnt target genes like c-myc, cyclinD1 and tumor survival [3]
We focused on Gal.3 and lymphoid enhancer factor 1 (LEF1), which have been described as key mediators of Wnt pathway in which dysregulation of this pathway has been associated with AML pathogenesis and prognosis
LEF1 expression and serum galectin.3 in AML patients were signi cantly higher than control
Summary
Introduction eWnt signaling is critically involved in normal haematopoietic development and self-renewal process of haematopoieic stem cells (HSCs) [1]. e Wnt signaling pathway is frequently dysregulated leading to more cancer susceptibility [2].e function of β catenin is under control of Wnt pathway, in case of absence of Wnt ligand, β catenin will be primed for degradation by proteasomes through its phosphorylation by destruction complex (GSK3β, CK1, Axin and APC), on the other hand when Wnt ligand binds its receptor (Frizzled and LRP5/6) the level of indestructible phosphorylated β catenin will increase saturation of the dendritic cells (DC) leading to cytosolic accumulation of nonphosphorylated β-catenin which translocate to the nucleus forming complexes with the T-cell factor (TCF)/lymphoid enhancer factor (LEF) transcriptional regulators and promotes activation of proto-oncogenic Wnt target genes like c-myc, cyclinD1 and tumor survival [3].Galectin-3 (gal-3) is a glycoprotein that has a role in brosis, in ammation, and cancer [4]. LEF1 expression dysregulation have a more complex role independent of Wnt signaling result in several disease patterns. While patients with higher Gal-3 levels characterized by poor risk ( = 0.02) than lower Gal. lels, more likely to carry a FLT3-ITD with borderline signi cance ( = 0.054). Combined LEF1high/Gal. low patients had lower baseline blast percentages ( = 0.02), favorable risk ( = 0.01), less likely to carry FLT3-ITD ( = 0.02), higher CR rate ( = 0.055), shorter time to CR (0.001) than other groups. We conclude that high LEF1 expression was a favorable prognostic marker which can de ne AML patient risk and outcome independent from assessing the serum galectin. level
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