Objective and Rationale Non-Hodgkin lymphomas (NHL) are a heterogeneous group of lymphoproliferative malignancies with variable patterns of behavior and responses to treatment. Although at present a significant number of high grade lymphoma patients can be cured with intensive regimens of cytotoxic and immunotherapeutic drugs, still these patients may relapse or become resistant to treatment. Therefore, there is a need to identify novel factors involved in lymphoma development and progression and hopefully to be used as targeted therapies. Thus, the objective of the present study was to explore the potential involvement of Yin Yang 1 (YY1) in the development as well as in the prognosis of NHL.
Hypothesis Our previous studies showed that YY1 is overexpressed in several human cancer cell lines and its expression correlates with resistance to chemo- immune-mediated apoptosis. Prognostic and diagnostic significance of YY1 has been recently shown in prostate cancer. Thus, we hypothesized that YY1 overexpression in NHL may be involved in transformation and act as a prognostic biomarker.
Methods and Designs Overexpression of YY1 has been shown by western blot and RT-PCR in NHL cell lines compared to normal B-cells. Validation of in vitro results has been performed by immunohistochemistry (IHC) and bioinformatics in NHL tissues. IHC analyses were performed in two commercial NHL tissue arrays containing 104 samples.
Results Gene expression analysis and association with clinical features of the transcription factor YY1 were evaluated using three different datasets of publicly available microarray data from lymphoma tumor-biopsy specimens. By analyzing the data set (221 NHL and 25 normal B-cells) by Basso et al., (Nat Genet 37:382, 2005) higher YY1 transcript levels were found in lymphoma tissues (BL and DLBCL) in comparison to normal B-cells. No significant differences were found with the other lymphoma histotypes. This class comparison analysis revealed that YY1 could be involved in the transformation of B cells giving rise to high-grade lymphomas. Expression levels of YY1 were analyzed in association with the available main clinical and biological parameters using the expression data of two different high grade lymphoma studies with a total of approximately 400 samples (
Conclusions and Implications Overall, the findings reveal that YY1 is involved in lymphoma development and may be useful as a biomarker of NHL transformation as well as a potential target for therapeutic interventions.
Disclosures: No relevant conflicts of interest to declare.