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WNT3 and LEF1 as markers for diagnosis and survival prediction in chronic lymphocytic leukemia patients

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Summary

Background

The Wnt pathway is aberrantly activated in chronic lymphocytic leukemia (CLL) and contributes to the antiapoptotic and mitogenic characteristics of CLL cells. Lymphoid enhancer-binding factor‑1 (LEF1) acts as a mediator and key transcription factor of the Wnt/β-catenin pathway. LEF1 helps to regulate important genes involved in tumor cell death mechanisms.

Objective

To analyze the expression levels of Wnt signaling pathway member (WNT3) and its key mediator LEF1 in Egyptian CLL patients and to detect the potential use of these genes as markers of CLL outcome.

Methods

We quantified the expression levels of Wnt3 and LEF1 in peripheral blood mononuclear cells of 30 untreated CLL and 19 healthy controls by qRT-PCR (quantitative real time polymerase chain reaction).

Results

Our study demonstrated significant upregulation of both Wnt3 and LEF1 in CLL (P < 0.0001). WNT3 and LEF1 were significantly decreased in CLL patients with ECOG performance 2 and 3 than those with 0 and 1 (p = 0.023 and 0.007, respectively). CLL patients with 17p deletion express significantly low LEF1 (p = 0.033). Low levels of WNT3 and LEF1 expression indicated a shorter overall survival (P = 0.007, 0.005, respectively). The predictive power of WNT3 and LEF1 expression showed good discrimination of CLL patients from controls (AUC >0.9).

Conclusion

Upregulation of WNT3 and LEF1 could be used as helpful and specific markers to distinguish our CLL patients. Low WNT3 and LEF1 expression is associated with shortened survival in CLL patients. These results indicate that WNT3 and LEF1 represent an attractive therapeutic target for future therapies in Egyptian CLL patients.

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Author information

Authors and Affiliations

  1. Hematology Unit, Oncology Center, Mansoura University, Mansoura, Egypt

    Manal Atef & Noha Eisa

  2. Hematology section, Clinical Pathology Department, Faculty of Medicine, Mansoura University, PO Box 35516, Mansoura, Egypt

    Layla M. Saleh MD/PhD

  3. Medical Oncology Unit, Oncology Center, Mansoura University, Mansoura, Egypt

    Sameh Shamaa

Authors
  1. Manal Atef
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  2. Layla M. Saleh MD/PhD
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Contributions

Sameh Shamaa, Layla M. Saleh, Noha Eisa and Manal Atef designed the study. Layla M. Saleh performed experiments. Sameh Shamaa, Layla M. Saleh, Noha Eisa and Manal Atef analyzed the data and wrote the manuscript. Sameh Shamaa, Layla M. Saleh and Noha Eisa assisted in editing the manuscript.

Corresponding author

Correspondence to Layla M. Saleh MD/PhD.

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M. Atef, L.M. Saleh, N. Eisa, and S. Shamaa declare that they have no competing interests.

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Atef, M., Saleh, L.M., Eisa, N. et al. WNT3 and LEF1 as markers for diagnosis and survival prediction in chronic lymphocytic leukemia patients. memo 16, 268–274 (2023). https://doi.org/10.1007/s12254-020-00651-8

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  • DOI: https://doi.org/10.1007/s12254-020-00651-8

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