Differential Expression of LEF1 Isoforms in Adult Lymphoid and Myeloid Malignancies

Abstract

Objective: Lymphoid enhancer-binding factor-1 (LEF1) is one of the key regulators of lymphocyte proliferation and its aberrant expression is a prognostic factor for lymphoid or myeloid malignancies. In this study, we focused on the expression of LEF1 isoforms in several hematological malignancies and found tissue-specific differential expression for the full-length (FL)-LEF1 gene and its tumor suppressor (∆LEF1) variant. Material and Method: Fifty-three leukemia/lymphoma patients were included in this study. Diagnostic samples of “lymphoid group” patients: Chronic Lymphoblastic Leukemia (CLL) (n=10), B-cell Acute Lymphoblastic Leukemia (B-ALL) (n=9) and “myeloid group” patients: Chronic Myeloblastic Leukemia (CML) (n=12), Acute Myeloid Leukemia (AML) (n=13), and Multiple Myeloma (MM) (n=9) were studied. Healthy bone marrow, peripheral blood cells, and CD34 positive cells were used as controls. Total (T) and FL-LEF1 transcript levels were examined by using quantitative real-time polymerase chain reaction (qRT-PCR). T and FL-LEF1 mRNA ratios were also evaluated for calculation of ∆LEF1. Results: LEF1 levels were significantly high in lymphoid malignancies, but MM and AML patients have decreased LEF1 levels. Although CLL patients have high FL-LEF1 levels, the ratio of the T/FL levels was significantly decreased. Conclusion: LEF1 is a proliferation factor for lymphocytes and not only its differential overexpression but also the ratio of T/FL isoforms seem to accompany leukemia progress.