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Medical Oncology

, 36:3 | Cite as

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

  • Luma Dayane de Carvalho Filiú-Braga
  • Teresa Raquel Tavares Serejo
  • Antonio Roberto Lucena-Araujo
  • Francisco Assis Rocha Neves
  • Juliana Lott de Carvalho
  • Eduardo Magalhaes Rego
  • Felipe Saldanha-AraujoEmail author
Short Communication
  • 88 Downloads

Abstract

The 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 of KDM4 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 of KDM4 members in CLL are still unknown. Here, we assessed the gene expression profile of KDM4A, KDM4B, and KDM4C 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 the KDM4B transcript in relation to control cases, and no difference was detected in KDM4C expression. Furthermore, patients with positive expression of ZAP-70 had lower expression of KDM4B and KDM4C 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 of KDM4 members is dysregulated in CLL and impact the prognosis of this leukemia. These findings are useful for a better understanding of the impact of epigenetics on CLL progression.

Keywords

KDM4 Chronic lymphocytic leukemia Prognostic factors ZAP-70 Karyotype 

Notes

Acknowledgements

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), and Fundação de Amparo à Pesquisa do Distrito Federal (FAPDF).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval and informed consent

The study was approved by the Ethical Committee of the Medical School Hospital of Ribeirão Preto, University of São Paulo, Brazil, and samples were collected after informed consent was obtained from patients and health donors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Luma Dayane de Carvalho Filiú-Braga
    • 1
  • Teresa Raquel Tavares Serejo
    • 1
  • Antonio Roberto Lucena-Araujo
    • 2
  • Francisco Assis Rocha Neves
    • 1
  • Juliana Lott de Carvalho
    • 3
  • Eduardo Magalhaes Rego
    • 4
  • Felipe Saldanha-Araujo
    • 1
    Email author
  1. 1.Laboratório de Farmacologia MolecularUniversidade de BrasíliaBrasíliaBrazil
  2. 2.Laboratório de HematologiaUniversidade Federal de PernambucoRecifeBrazil
  3. 3.Laboratório de BiotecnologiaUniversidade Católica de BrasíliaBrasíliaBrazil
  4. 4.Laboratório de HematologiaUniversidade de São PauloRibeirão PrêtoBrazil

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