Investigating the prognostic importance of wwox in hematological malignancies

The WW domain-containing oxidoreductase (WWOX) gene is located on chromosome 16q23.3-q24.1 and contains the common chromosomal fragile site, FRA16D. The WWOX gene encodes a Wwox tumor suppressor protein with a molecular weight of 46 kDa. Loss of heterozygosity (LOH) at the WWOX locus, promoter hypermethylation of the WWOX promoter, and consequently Wwox expression loss or reduction has been reported in a large fraction of many human cancers. Also, recent studies have shown that Wwox deficiency is associated with poor prognosis in various types of cancer. WWOX expression levels could be a possible biomarker for chronic lymphocytic leukemia (CLL). Clinical features and genetic anomalies of CLL are well defined, but molecular details are still under investigation. As much as we know, there is no evidence for diagnostic and prognostic significance of Wwox in CLL. In our study, we aimed to define the expression levels of WWOX in CLL patients and also to analyze the WWOX expression in CLL patients with regard to their clinical characteristics. We performed this study in 40 CLL patients and 26 healthy controls. We analyzed the WWOX expression levels by using reverse transcriptase-quantitative PCR (RT-QPCR). Our results showed that WWOX expression was significantly higher in CLL patients compared to healthy control group (P<0.001). We did not find any statistically significant difference between WWOX levels and clinical parameters in CLL (P>0.05). In conclusion, abnormal transcription variants of WWOX gene can be associated with abnormal protein isoforms and these isoforms can change the tumor suppressive effects of WWOX gene in CLL patients. Key words: Chronic lymphocytic leukemia, tumor suppressor, WWOX