Reduced expression of the WW domain-containing oxidoreductase in human hematopoietic malignancies
Lingqing Luo1, Yan Chen1, Xiao Cheng2
1Department of Clinical Laboratory, Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Provincial Cancer Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian 350014, P.R. China.
Abstract:
The role of the WW domain-containing oxidoreductase (WWOX) gene in multiple types of solid human cancers has been documented extensively thus far. Recently, we investigated the in vitro effects of WWOX overexpression and observed marked growth arrest in human leukemia cells; however, the clinical characterization of WWOX in leukemia remains poorly investigated. The present study evaluated the WWOX expression profiles of 182 patients with leukemia of different types and 5 leukemic cell lines, using reverse transcription-polymerase chain reaction and immunofluorescence analysis. The results found that WWOX mRNA and WWOX protein expression was significantly reduced or absent in the leukemia cases and cell lines compared with paired controls. The WWOX-positive rate was also lower in the leukemia cases compared with the rate of the normal controls. Notably, the WWOX level was reduced in newly diagnosed and relapsed cases, or in chronic myelogenous leukemia in the blastic phase, yet elevated in remission samples. Moreover, WWOX-negative cases exhibited WWOX expression restoration following induced remission. These findings suggest that WWOX may contribute to the occurrence and development of leukemia, and that it has potential to be a good biomarker or predictor for leukemia therapy.
Insights
The WW domain-containing oxidoreductase (WWOX) gene is significantly reduced in leukemia patients and cell lines. WWOX levels may serve as a biomarker for leukemia diagnosis and therapy prediction.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The WW domain-containing oxidoreductase (WWOX) gene is implicated in various solid human cancers.
- Its role in leukemia, particularly clinical characterization, is less understood.
- Previous in vitro studies showed WWOX overexpression induces growth arrest in leukemia cells.
Purpose of the Study:
- To evaluate WWOX expression profiles in leukemia patients and cell lines.
- To investigate the potential of WWOX as a biomarker for leukemia therapy.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze WWOX mRNA levels.
- Immunofluorescence analysis was performed to assess WWOX protein expression.
- Study included 182 leukemia patients and 5 leukemic cell lines, with comparisons to normal controls.
Main Results:
- WWOX mRNA and protein expression were significantly reduced or absent in leukemia cases and cell lines compared to controls.
- The WWOX-positive rate was lower in leukemia patients than in normal controls.
- WWOX levels were reduced in newly diagnosed, relapsed, and blastic phase chronic myelogenous leukemia, but elevated in remission samples. WWOX expression was restored in negative cases following induced remission.
Conclusions:
- Reduced WWOX expression suggests its involvement in the occurrence and development of leukemia.
- WWOX demonstrates potential as a diagnostic biomarker and predictor for leukemia therapy.
- Restoration of WWOX expression in remission highlights its dynamic role in the disease course.
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