Is Klotho Gene a Biomarker to Pathogenesis of Myelodysplastic Syndrome in Elderly Patient? A New Hypothesis

Abstract

An important new biomarker for cancer is the Klotho, an anti-aging target, associated to proliferation and apoptosis of tumor cells. In this study, we hypothesized that the Myelodysplastic syndrome (MDS) pathogenesis, an elderly hematopoietic disease, can be affect by block of the Klotho expression, increasing ROS production in the medullary microenvironment, attenuating the DNA damage in HSCs, and leading to reduced count of blood cell precursors, characterizing the cytopenic profile of MDS patient. The absence or negative regulation of Klotho may be a poor prognostic marker of MDS, especially when patients are stratified by age. We believed that younger adult MDS patients show a higher Klotho expression while compared to old adults MDS patients, demonstrating that its expression is decreased with increasing age, representing a more aggressive disease. To confirm this hypothesis, an extensive clinical case-control study can be performed on bone marrow cell samples of MDS patients to show differential expression of Klotho gene and protein, and as this target can be modulate in this disease (based on promoter region methylation analysis). These approaches may define the Klotho as a new pathologic marker to MDS in elderly and improve future potential therapies.