Unraveling KDM4 histone demethylase expression and its association with adverse cytogenetic findings in chronic lymphocytic leukemia

AbstractThe acquisition of complex karyotypes is related to the progression of chronic lymphocytic leukemia (CLL) and patients with this condition have a poor prognosis. Despite recent advances in the classification of prognosis in CLL patients, understanding of the molecular mechanisms that lead to genomic instability and progression of this disease remains inadequate. Interestingly, dysregulated expression ofKDM4 members is involved in the progression of several cancer types and plays a role in the DNA damage response; however, the gene expression profile and the importance ofKDM4 members in CLL are still unknown. Here, we assessed the gene expression profile ofKDM4A, KDM4B, andKDM4C in 59 CLL samples and investigated whether these histone demethylases have any influence on the prognostic markers of this leukemia.KDM4A gene expression was higher in CLL patients as compared with control samples. In contrast, CLL samples showed decreased levels of theKDM4B transcript in relation to control cases, and no difference was detected inKDM4C expression. Furthermore, patients with positive expression of ZAP-70 had lower expression ofKDM4B andKDM4C as compared with ZAP-70-negative patients. More importantly, patients with low expression of these histone demethylases had higher leukemic cell numbers and displayed adverse cytogenetic findings and the acquisition of a complex karyotype. The present data clearly show that the expression ofKDM4 members is dysregulated in CLL and impact the...
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research