Prognostic Impact of Lymphoid Enhancer Factor 1 Expression and Serum Galectin.3 in Egyptian AML Patients

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, LEF1high expression 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.

The multiple ways Wnt signaling contributes to acute leukemia pathogenesis

“…This crosstalk can be crucial in therapy resistance and minimal residual disease, with galectins being important messengers. Galectin‐3 levels were described as an independent adverse prognostic biomarker in AML 156,157 . The co‐culture with human bone marrow‐derived mesenchymal stromal cells (hBM‐MSCs) induces Galectin‐3 expression in AL cells, leading to β‐catenin stabilization mediated by AKT and GSK3β phosphorylation and was necessary for resistance against cytotoxic drugs 158 .…”