Chronic lymphocytic leukemia patients with heterogeneously or fully methylated LPL promotor display longer time to treatment

Iben Daugaard; Dianna Hussmann; Louise Kristensen; Thomas Kristensen; Tina E Kjeldsen; Charlotte G Nyvold; Thomas S Larsen; Michael B Møller; Lise Lotte Hansen; Tomasz K Wojdacz

doi:10.2217/epi-2018-0020

Chronic lymphocytic leukemia patients with heterogeneously or fully methylated LPL promotor display longer time to treatment

Iben Daugaard, Dianna Hussmann, Louise Kristensen, Thomas Kristensen, Tina E Kjeldsen, Charlotte G Nyvold, Thomas S Larsen, Michael B Møller, Lise Lotte Hansen, Tomasz K Wojdacz

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

4 Citations (Scopus)

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.

Original language	English
Journal	Epigenomics
Volume	10
Issue	9
Pages (from-to)	1155-1166
Number of pages	12
ISSN	1750-1911
DOIs	https://doi.org/10.2217/epi-2018-0020
Publication status	Published - Sept 2018

Keywords

CLL
MS-HRM
biomarker
chronic lymphocytic leukemia
heterogeneous methylation
treatment

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@article{9fd7b777a4ff45ff83d8ce173d09a054,

title = "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 = "CLL, MS-HRM, biomarker, chronic lymphocytic leukemia, heterogeneous methylation, treatment",

author = "Iben Daugaard and Dianna Hussmann and Louise Kristensen and Thomas Kristensen and Kjeldsen, {Tina E} and Nyvold, {Charlotte G} and Larsen, {Thomas S} and M{\o}ller, {Michael B} and Hansen, {Lise Lotte} and Wojdacz, {Tomasz K}",

year = "2018",

month = sep,

doi = "10.2217/epi-2018-0020",

language = "English",

volume = "10",

pages = "1155--1166",

journal = "Epigenomics",

issn = "1750-1911",

publisher = "Taylor and Francis Ltd.",

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}

Chronic lymphocytic leukemia patients with heterogeneously or fully methylated LPL promotor display longer time to treatment. / Daugaard, Iben; Hussmann, Dianna; Kristensen, Louise et al.
In: Epigenomics, Vol. 10, No. 9, 09.2018, p. 1155-1166.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Chronic lymphocytic leukemia patients with heterogeneously or fully methylated LPL promotor display longer time to treatment

AU - Daugaard, Iben

AU - Hussmann, Dianna

AU - Kristensen, Louise

AU - Kristensen, Thomas

AU - Kjeldsen, Tina E

AU - Nyvold, Charlotte G

AU - Larsen, Thomas S

AU - Møller, Michael B

AU - Hansen, Lise Lotte

AU - Wojdacz, Tomasz K

PY - 2018/9

Y1 - 2018/9

N2 - 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.

AB - 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.

KW - CLL

KW - MS-HRM

KW - biomarker

KW - chronic lymphocytic leukemia

KW - heterogeneous methylation

KW - treatment

U2 - 10.2217/epi-2018-0020

DO - 10.2217/epi-2018-0020

M3 - Journal article

C2 - 30182737

SN - 1750-1911

VL - 10

SP - 1155

EP - 1166

JO - Epigenomics

JF - Epigenomics

IS - 9

ER -

Chronic lymphocytic leukemia patients with heterogeneously or fully methylated LPL promotor display longer time to treatment

Abstract

Keywords

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