Chronic Lymphocytic Leukemia Patients with Heterogeneously or Fully Methylated LPL Promotor Display Longer Time to Treatment

Abstract

Aim: We investigated whether DNA methylation regulates expression of LPL and PI3K complex genes in chronic lymphocytic leukemia (CLL) and evaluated the prognostic significance of LPL promoter methylation in CLL patients. Patients & methods: Methylation of LPL promoter was assessed in 112 patients using methylation-sensitive high-resolution melting (MS-HRM).Results: Patients with a fully or heterogeneously methylated LPL promoter had significantly longer median time to treatment (p < 0.001) and 75% lower (hazard ratio: 0.25; 95% CI: 0.15–0.42; p < 0.001) risk of requirement for treatment as opposed to patients with nonmethylated promoter. Multivariate modeling confirmed independent prognostic value of these findings. Conclusion: Chronic lymphocytic leukemia patients with a fully or heterogeneously methylated LPL gene promoter display indolent disease course and acquisition of heterogeneous methylation of LPL promoter is insufficient to induce gene expression.

Keywords::

• biomarker
• chronic lymphocytic leukemia
• CLL
• heterogeneous methylation
• MS-HRM
• treatment

Financial & competing interests disclosure

Aarhus Institute of Advanced Studies, Arvid Nilssons Foundation, Region of Southern Denmark, Beckett Foundation, Danielsens Foundation, the University of Southern Denmark and Odense University Hospital supported the project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The Ethics Committee of Region of Southern Denmark approved the study, under approval number: S-20100128.

Additional information

Funding

Aarhus Institute of Advanced Studies, Arvid Nilssons Foundation, Region of Southern Denmark, Beckett Foundation, Danielsens Foundation, the University of Southern Denmark and Odense University Hospital supported the project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.