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Long intergenic non-coding RNA-p21 is associated with poor prognosis in chronic lymphocytic leukemia

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Abstract

Background

Long non-coding RNAs (LncRNAs) are RNA transcripts longer than 200 nucleotides. They are new players in transcriptional regulation and cancer research. LincRNA-p21 is a p53-regulated lncRNA involved in the p53 transcriptional network. It has an important role in regulating cellular proliferation and apoptosis. Chronic lymphocytic leukemia is derived by a typical defect in apoptosis and characterized by clonal proliferation and accumulation of mature B cells. The aim of the present study was to assess the expression pattern of the lincRNA-p21 and investigate its potential role as a new prognostic marker in CLL.

Methods

The study was conducted on 80 newly diagnosed CLL patients and 80 age- and sex-matched controls. The analysis of LincRNA-p21 and the p53 downstream proapoptotic target genes (MDM2, PUMA, BAX, and NOXA) was performed by real-time PCR. The cytogenetic abrasions and expression of ZAP70 and CD38 were detected by FISH and Flow cytometry, respectively.

Results

LincRNA-p21 was significantly downregulated in CLL patients compared to controls. The downstream proapoptotic targets were significantly downregulated in CLL patients and positively correlated with lincRNA-p21. Low expression of lincRNA-p21 was associated with poor prognostic markers (advanced stages of CLL, del 17p13, ZAP70, and CD38 expression), failure of complete remission, shorter progression free survival, and overall survival. Low lincRNA-p21 expression was independently prognostic for shorter time to treatment.

Conclusion

Low expression of lincRNA-p21 demarcates a more aggressive form of CLL with poor prognosis. Therefore, it could be considered as a new prognostic marker to predict disease outcome in CLL.

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Acknowledgements

Authors would like to thank all the patients and their families for participating in this project. Also, authors acknowledge the Molecular Biology Research Lab team in MRC of Alexandria Faculty of Medicine.

Funding

Self-funding from the authors and co-authors.

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Authors and Affiliations

  1. Clinical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt

    R. Abo Elwafa

  2. Internal Medicine Department (Hematology Unit), Faculty of Medicine, Alexandria University, Alexandria, Egypt

    A. Abd Elrahman & O. Ghallab

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  1. R. Abo Elwafa
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  2. A. Abd Elrahman
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Correspondence to R. Abo Elwafa.

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The study was conducted after approval of the Medical Ethics Committee of Alexandria Faculty of Medicine.

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All study participants gave written informed consents after explaining the nature, steps and aim of the study.

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Abo Elwafa, R., Abd Elrahman, A. & Ghallab, O. Long intergenic non-coding RNA-p21 is associated with poor prognosis in chronic lymphocytic leukemia. Clin Transl Oncol 23, 92–99 (2021). https://doi.org/10.1007/s12094-020-02398-4

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  • DOI: https://doi.org/10.1007/s12094-020-02398-4

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