Lymphoid enhancer-binding factor 1 (LEF-1) is a crucial transcription factor that functions as a key nuclear mediator of WNT/_-catenin signaling, responsible for regulating cell proliferation and survival. LEF-1 has an important role in lymphopoiesis, and is typically expressed in T cells and B cell precursors. Differentiation into mature B and plasma cells downregulates LEF-1 expression. In normal lymphoid tissues, LEF-1 is nuclear localized and observed predominantly in T cells of the paracortical regions; staining was undetected in B cells.

LEF-1 expression has been reported in a variety of cases of leukemia and lymphoma. Gene expression profiling revealed overexpression of LEF-1 in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). In one study, LEF-1 immunostaining was detected in all neoplastic cells of 92 CLL/SLL cases. LEF-1 was identified in 50% of high grade follicular lymphoma and 38% of diffuse large B-cell lymphoma, but not in mantle cell lymphoma or marginal zone lymphoma. Recently, high LEF-1 was demonstrated as a favorable prognostic marker in cytogenetically normal acute myeloid leukemia. Due to its high sensitivity, LEF-1 has been proposed to be a suitable immunohistochemical marker for diagnosis and differential diagnosis for CLL/SLL. Recent studies have expanded upon the role of LEF-1. Alternately spliced isoforms may play additional roles in regulating cell growth in colon carcinoma, and nuclear LEF-1 immunostaining was detected in 36% of adenocarcinoma brain metastases.