Epigenetic changes as a novel tool for prognostic stratifying chronic lymphocytic leukaemia
Authors:
L. Poppová; K. Plevová; Š. Pospíšilová
Authors‘ workplace:
CEITEC – Středoevropský technologický institut, Masarykova univerzita, Brno
Published in:
Transfuze Hematol. dnes,23, 2017, No. 4, p. 210-214.
Category:
Overview
Chronic lymphocytic leukaemia (CLL) is a clonal B lymphocyte malignancy with a highly heterogeneous course. Some patients remain asymptomatic and do not require treatment for many years, while patients with aggressive forms of the disease require therapy soon after diagnosis. Recently, evidence has been growing about the important role of methylations in natural evolution as well as in the development of various diseases including cancer. Whole genome sequencing has revealed that in CLL, similarly to other malignancies, aberrant methylations arise in the early phases of the disease. CLL patients have diverse methylation profiles and the methylation status of certain loci correlates with disease aggressiveness. In this brief report, we focus on methylation changes and their role in CLL prognosis.
Key words:
chronic lymphocytic leukaemia – CLL – epigenetics – methylations – prognosis – differentiation
Sources
1. Dameshek W. Chronic lymphocytic leukemia – an accumulative disease of immunologically incompetent lymphocytes. Blood 1967;29(4): 566–584.
2. Caligaris-Cappio F, Ghia P. The normal counterpart to the chronic lymphocytic leukemia B cell. Best Pract Res Clin Haematol 2007;20(3): 385–397.
3. Damle BRN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999;94(6): 1840–1847.
4. Hamblin BTJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig VH genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999;94(6): 1848–1854.
5. Doehner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000;343(26): 1910–1916.
6. Delgado J, Doubek M, Baumann T, et al. Chronic lymphocytic leukemia: A prognostic model comprising only two biomarkers (IGHV mutational status and FISH cytogenetics) separates patients with different outcome and simplifies the CLL-IPI. Am J Hematol; publikováno elektronicky 13. února 2017. DOI: 10.1002/ajh.24660.
7. Bird AP. CpG-rich islands and the function of DNA methylation. Nature 1986;321(6067): 209–213.
8. Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U. S. A. 2006;103(5): 1412–1417.
9. Illingworth RS, Bird AP. CpG islands – “A rough guide.” FEBS Lett 2009;583(11): 1713–1720.
10. Goll MG, Bestor TH. Eukaryotic cytosine methyltransferases. Ann Rev Biochem 2005;74(1): 481–514.
11. Liu L, Wylie RC, Andrews LG, Tollefsbol TO. Aging, cancer and nutrition: the DNA methylation connection. Mech Ageing Dev 2003;124(10–12): 989–998.
12. Oakes CC, Seifert M, Assenov Y, et al. DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia. Nat Genet 2016;48(3): 253–264.
13. Kulis M, Heath S, Bibikova M, et al. Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia. Nat Genet 2012;44(11): 1236–1242.
14. Queirós AC, Villamor N, Clot G, et al. A B-cell epigenetic signature defines three biological subgroups of chronic lymphocytic leukemia with clinical impact. Leukemia 2015;29(29): 598–605.
15. Tobin G, Thunberg U, Karlsson K, et al. Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia. Blood 2004;104(9): 2879–2885; 2017;104(9): 2879–2886.
16. Bhoi S, Mansouri L, Castellano G, et al. DNA methylation profiling in chronic lymphocytic leukemia patients carrying stereotyped B-cell receptors: a different cellular origin for subset. Haematologica 2017;102(S2): 68(Abstract P244).
17. Corcoran M, Parker A, Orchard J, et al. ZAP-70 methylation status is associated with ZAP-70 expression status in chronic lymphocytic leukemia. Haematologica 2005;90: 1078–1088.
18. Rani L, Mathur N, Gupta R, et al. Genome-wide DNA methylation profiling integrated with gene expression profiling identifies PAX9 as a novel prognostic marker in chronic lymphocytic leukemia. Clin Epigenetics 2017;9(1): 57.
19. Subhash S, Andersson P-O, Kosalai ST, et al. Global DNA methylation profiling reveals new insights into epigenetically deregulated protein coding and long noncoding RNAs in CLL. Clin Epigenetics 2016;8(1): 106.
20. Cortese D, Sutton L, Cahill N, et al. On the way towards a “CLL prognostic index”: focus on TP53, BIRC3, SF3B1, NOTCH1 and MYD88 in a population-based cohort. Leukemia 2014;28(3): 710–713.
21. Cahill N, Bergh A-C, Kanduri M, et al. 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 2013;27(1): 150–158.
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Haematology Internal medicine Clinical oncologyArticle was published in
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