WNT6 mRNA Is Overexpressed in Variuos Non-Hodgkin’s Lymphoma Cases with No Apparent Relation to Cyclin D1 Level.

A casual role for Wnts in the development of some human cancers seems to be established. Binding of Wnt to its receptor results in β-catenin stabilization and in consequence, translocation to the nucleus, where it activates the specific target gene’s expression including CCND1 (cyclin D1). Abnormal levels of β-catenin may therefore contribute to neoplastic transformation by causing accumulation of cyclin D1. Overexpression of cyclin D1, as a result of the t(11;14)(q13;q32) translocation, which places cyclin D1 gene under the enhancer of immunoglobulin heavy chain is considered the hallmark of mantle cell lymphoma (MCL) but high levels of cyclin D1 have also been observed with various levels in some cases of non-MCL lymphoproliferative disorders not involving t(11;14), such as hairy cell leukemia (HCL), splenic lymphoma with villous lymphocytes (SLVL), prolymphocytic leukemia (PLL) and some atypical CLL cases. Little is known about potential Wnt signaling in mature lymphocytes or lymphoid malignancies. Recent finding, that the Wnt pathway regulates the proliferation and survival of normal B lymphocytes, together with WNT16 overexpression in leukemic cell lines and high expression of five other Wnts including WNT6 in CLL suggests that Wnt family members can contribute to tumorgenesis in the immune system. In the current study we evaluated the relationship between Wnts and cyclin D1 mRNA expression level in NHL patients. WNT6 and CCND1 mRNA expression level normalized to 18 sRNA was evaluated by RT-PCR on 200 biopsy samples taken from 150 lymphoma patients. In parallel, samples underwent pathological and flow cytometry examination. WNT6 mRNA was detected in all specimens tested. The 18 sRNA/WNT6 ratio ranged from 1 to 650. Most of the CLL specimens were among those with high WNT6 mRNA expression, but no apparent correlation between the level of WNT6 mRNA expression and cyclin D1 status was found so far.