450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments

Research output: Contribution to journalArticle

Standard

450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments. / Cahill, N.; Bergh, A-C; Kanduri, M.; Goransson-Kultima, H.; Mansouri, L.; Isaksson, A.; Ryan, F.; Smedby, K. E.; Juliusson, Gunnar; Sundstrom, C.; Rosen, A.; Rosenquist, R.

In: Leukemia, Vol. 27, No. 1, 2013, p. 150-158.

Research output: Contribution to journalArticle

Harvard

Cahill, N, Bergh, A-C, Kanduri, M, Goransson-Kultima, H, Mansouri, L, Isaksson, A, Ryan, F, Smedby, KE, Juliusson, G, Sundstrom, C, Rosen, A & Rosenquist, R 2013, '450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments', Leukemia, vol. 27, no. 1, pp. 150-158. https://doi.org/10.1038/leu.2012.245

APA

CBE

Cahill N, Bergh A-C, Kanduri M, Goransson-Kultima H, Mansouri L, Isaksson A, Ryan F, Smedby KE, Juliusson G, Sundstrom C, Rosen A, Rosenquist R. 2013. 450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments. Leukemia. 27(1):150-158. https://doi.org/10.1038/leu.2012.245

MLA

Vancouver

Author

Cahill, N. ; Bergh, A-C ; Kanduri, M. ; Goransson-Kultima, H. ; Mansouri, L. ; Isaksson, A. ; Ryan, F. ; Smedby, K. E. ; Juliusson, Gunnar ; Sundstrom, C. ; Rosen, A. ; Rosenquist, R. / 450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments. In: Leukemia. 2013 ; Vol. 27, No. 1. pp. 150-158.

RIS

TY - JOUR

T1 - 450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments

AU - Cahill, N.

AU - Bergh, A-C

AU - Kanduri, M.

AU - Goransson-Kultima, H.

AU - Mansouri, L.

AU - Isaksson, A.

AU - Ryan, F.

AU - Smedby, K. E.

AU - Juliusson, Gunnar

AU - Sundstrom, C.

AU - Rosen, A.

AU - Rosenquist, R.

PY - 2013

Y1 - 2013

N2 - In chronic lymphocytic leukemia (CLL), the microenvironment influences gene expression patterns; however, knowledge is limited regarding the extent to which methylation changes with time and exposure to specific microenvironments. Using high-resolution 450K arrays, we provide the most comprehensive DNA methylation study of CLL to date, analyzing paired diagnostic/follow-up samples from IGHV-mutated/untreated and IGHV-unmutated/treated patients (n = 36) and patient-matched peripheral blood and lymph node samples (n = 20). On an unprecedented scale, we revealed 2239 differentially methylated CpG sites between IGHV-mutated and unmutated patients, with the majority of sites positioned outside annotated CpG islands. Intriguingly, CLL prognostic genes (for example, CLLU1, LPL, ZAP70 and NOTCH1), epigenetic regulator (for example, HDAC9, HDAC4 and DNMT3B), B-cell signaling (for example, IBTK) and numerous TGF-beta and NF-kappa B/TNF pathway genes were alternatively methylated between subgroups. Contrary, DNA methylation over time was deemed rather stable with few recurrent changes noted within subgroups. Although a larger number of non-recurrent changes were identified among IGHV-unmutated relative to mutated cases over time, these equated to a low global change. Similarly, few changes were identified between compartment cases. Altogether, we reveal CLL subgroups to display unique methylation profiles and unveil methylation as relatively stable over time and similar within different CLL compartments, implying aberrant methylation as an early leukemogenic event. Leukemia (2013) 27, 150-158; doi:10.1038/leu.2012.245

AB - In chronic lymphocytic leukemia (CLL), the microenvironment influences gene expression patterns; however, knowledge is limited regarding the extent to which methylation changes with time and exposure to specific microenvironments. Using high-resolution 450K arrays, we provide the most comprehensive DNA methylation study of CLL to date, analyzing paired diagnostic/follow-up samples from IGHV-mutated/untreated and IGHV-unmutated/treated patients (n = 36) and patient-matched peripheral blood and lymph node samples (n = 20). On an unprecedented scale, we revealed 2239 differentially methylated CpG sites between IGHV-mutated and unmutated patients, with the majority of sites positioned outside annotated CpG islands. Intriguingly, CLL prognostic genes (for example, CLLU1, LPL, ZAP70 and NOTCH1), epigenetic regulator (for example, HDAC9, HDAC4 and DNMT3B), B-cell signaling (for example, IBTK) and numerous TGF-beta and NF-kappa B/TNF pathway genes were alternatively methylated between subgroups. Contrary, DNA methylation over time was deemed rather stable with few recurrent changes noted within subgroups. Although a larger number of non-recurrent changes were identified among IGHV-unmutated relative to mutated cases over time, these equated to a low global change. Similarly, few changes were identified between compartment cases. Altogether, we reveal CLL subgroups to display unique methylation profiles and unveil methylation as relatively stable over time and similar within different CLL compartments, implying aberrant methylation as an early leukemogenic event. Leukemia (2013) 27, 150-158; doi:10.1038/leu.2012.245

KW - chronic lymphocytic leukemia

KW - DNA methylation

KW - 450K array

KW - prognostic

KW - subgroups

KW - compartments

U2 - 10.1038/leu.2012.245

DO - 10.1038/leu.2012.245

M3 - Article

VL - 27

SP - 150

EP - 158

JO - Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K

T2 - Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K

JF - Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K

SN - 1476-5551

IS - 1

ER -