Abstract
Acute myeloid leukemia (AML) is a malignant clonal disorder affecting myeloid differentiation through mechanisms that include epigenetic dysregulation. Abnormal changes in DNA methylation and gene expression profiles of pathways involved in hematopoietic development, such as Wnt/β-catenin, contribute to the transformation, development, and maintenance of leukemic cells. This review summarizes the alterations of Wnt signaling-related genes at the epigenetic and transcriptional level and their implications for AML prognosis. Among the implications of epigenetic alterations in AML, methylation of Wnt antagonists is related to poor prognosis, whereas their upregulation has been associated with a better clinical outcome. Furthermore, Wnt target genes c-Myc and LEF-1 present distinct implications. LEF-1 expression positively influences the patient overall survival. c-Myc upregulation has been associated with treatment resistance in AML, although c-Myc expression is not exclusively dependent of Wnt signaling. Understanding the signaling abnormalities could help us to further understand leukemogenesis, improve the current risk stratification for AML patients, and even serve to propose novel therapeutic targets.
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Acknowledgements
Authors thank to “Departamento Administrativo de Ciencia, Tecnología e Innovación-Colciencias” and “Instituto Tecnológico Metropolitano-ITM” for financial support within the program Jovenes Investigadores en Inovadores Colciencias-ITM (Grant call 706-2015. This work was also supported by Colciencias (Project Code: 115065743926, Grant call 657-2014) and Instituto Tecnológico Metropolitano-ITM (Project Code: P17214).
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This work was supported by Departamento Administrativo de Ciencia, Tecnología e Innovación-Colciencias under Grant 115065743926; and Instituto Tecnológico Metropolitano-ITM Grant P17214.
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Cardona-Echeverry, A., Prada-Arismendy, J. Deciphering the role of Wnt signaling in acute myeloid leukemia prognosis: how alterations in DNA methylation come into play in patients’ prognosis. J Cancer Res Clin Oncol 146, 3097–3109 (2020). https://doi.org/10.1007/s00432-020-03407-3
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DOI: https://doi.org/10.1007/s00432-020-03407-3