In CLL, cortactin positivity did correlate with LEF1 and CD200 expression, and the combined positivity for ≥2 markers strongly predicted CLL diagnosis.
Additionally, due to aberrant LEF1 activity resulting in cancer progression, knockdown and inhibition treatments designed to target LEF1 have proven effective in alleviating cancer growth, migration, and invasion in CLL, CRC, glioblastoma multiforme (GBM), and renal cell carcinoma (RCC).
The results of this study indicate that methylprednisolone can suppress Wnt signaling pathway by down-regulating LEF-1 protein expression, indicating a novel mechanism for HDMP therapy in CLL.
In contrast, chronic lymphocytic leukemia (CLL) cells show constitutionally active Wnt signaling, which is associated with upregulated levels of pathway members such as Wnt3 and lymphoid enhancer-binding factor-1.
Moreover, we identified lymphoid enhancer-binding factor 1 (LEF1), a downstream effector of the Wnt/β-catenin pathway, as a transcription repressor of CYLD in CLL.
These data support the notion that CLL can differentiate into ISC and that this triggers decreased leukemic cell survival secondary to the down regulation of LEF-1 and decreased Wnt pathway activation.
This study has identified the constitutive activation and prosurvival function of LEF-1 and the Wnt pathway in CLL and uncovered a possible role for these factors in the preleukemic state of monoclonal B-cell lymphocytosis.
This study demonstrates that although LEF-1 mRNA is universally, highly expressed in B-CLL, expression of this gene is much lower or absent in the majority of low-grade B-cell non-Hodgkin's lymphoma (NHL).
However, acute myeloid leukemia and acute lymphocytic leukemia showed a significantly increased fraction of the oncogenic LEF-1 compared with chronic lymphocytic leukemia and chronic myeloid leukemia.