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Erschienen in: memo - Magazine of European Medical Oncology 4/2023

13.10.2020 | original report

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

verfasst von: Manal Atef, Layla M. Saleh, MD/PhD, Noha Eisa, Sameh Shamaa

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 4/2023

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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.
Literatur
3.
Zurück zum Zitat Jelinek DF, Tschumper RC, Stolovitzky GA, Iturria SJ, Tu Y, Lepre J, et al. Identification of a global gene expression signature of B‑chronic lymphocytic leukemia. Mol Cancer Res. 2003;1:346–61.PubMed Jelinek DF, Tschumper RC, Stolovitzky GA, Iturria SJ, Tu Y, Lepre J, et al. Identification of a global gene expression signature of B‑chronic lymphocytic leukemia. Mol Cancer Res. 2003;1:346–61.PubMed
4.
Zurück zum Zitat Rosenwald A, Alizadeh AA, Widhopf G, Simon R, Davis RE, Yu X, et al. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med. 2001;194:1639–47.CrossRefPubMedPubMedCentral Rosenwald A, Alizadeh AA, Widhopf G, Simon R, Davis RE, Yu X, et al. Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med. 2001;194:1639–47.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Poppova L, Janovska P, Plevova K, Radova L, Plesingerova H, Borsky M, et al. Decreased WNT3 expression in chronic lymphocytic leukaemia is a hallmark of disease progression and identifies patients with worse prognosis in the subgroup with mutated IGHV. Br J Haematol. 2016;175:851–9. https://doi.org/10.1111/bjh.14312.CrossRefPubMed Poppova L, Janovska P, Plevova K, Radova L, Plesingerova H, Borsky M, et al. Decreased WNT3 expression in chronic lymphocytic leukaemia is a hallmark of disease progression and identifies patients with worse prognosis in the subgroup with mutated IGHV. Br J Haematol. 2016;175:851–9. https://​doi.​org/​10.​1111/​bjh.​14312.CrossRefPubMed
22.
Zurück zum Zitat Erdfelder F, Hertweck M, Filipovich A, Uhrmacher S, Kreuzer KA. High lymphoid enhancer-binding factor expression is associated with disease progression and poor prognosis in chronic lymphocytic leukemia. Hematol Rep. 2010;2:24–7. https://doi.org/10.4081/hr.2010.e3.CrossRef Erdfelder F, Hertweck M, Filipovich A, Uhrmacher S, Kreuzer KA. High lymphoid enhancer-binding factor expression is associated with disease progression and poor prognosis in chronic lymphocytic leukemia. Hematol Rep. 2010;2:24–7. https://​doi.​org/​10.​4081/​hr.​2010.​e3.CrossRef
Metadaten
Titel
WNT3 and LEF1 as markers for diagnosis and survival prediction in chronic lymphocytic leukemia patients
verfasst von
Manal Atef
Layla M. Saleh, MD/PhD
Noha Eisa
Sameh Shamaa
Publikationsdatum
13.10.2020
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 4/2023
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-020-00651-8

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