DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Gustafsson, Mats G
MetadataShow full item record
CitationBlood 2010, 115(6):1214-25
AbstractDespite improvements in the prognosis of childhood acute lymphoblastic leukemia (ALL), subgroups of patients would benefit from alternative treatment approaches. Our aim was to identify genes with DNA methylation profiles that could identify such groups. We determined the methylation levels of 1320 CpG sites in regulatory regions of 416 genes in cells from 401 children diagnosed with ALL. Hierarchical clustering of 300 CpG sites distinguished between T-lineage ALL and B-cell precursor (BCP) ALL and between the main cytogenetic subtypes of BCP ALL. It also stratified patients with high hyperdiploidy and t(12;21) ALL into 2 subgroups with different probability of relapse. By using supervised learning, we constructed multivariate classifiers by external cross-validation procedures. We identified 40 genes that consistently contributed to accurate discrimination between the main subtypes of BCP ALL and gene sets that discriminated between subtypes of ALL and between ALL and controls in pairwise classification analyses. We also identified 20 individual genes with DNA methylation levels that predicted relapse of leukemia. Thus, methylation analysis should be explored as a method to improve stratification of ALL patients. The genes highlighted in our study are not enriched to specific pathways, but the gene expression levels are inversely correlated to the methylation levels.
DescriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field
- Hypermethylation of the 5' CpG island of the FHIT gene is associated with hyperdiploid and translocation-negative subtypes of pediatric leukemia.
- Authors: Zheng S, Ma X, Zhang L, Gunn L, Smith MT, Wiemels JL, Leung K, Buffler PA, Wiencke JK
- Issue date: 2004 Mar 15
- Specific promoter methylation identifies different subgroups of MLL-rearranged infant acute lymphoblastic leukemia, influences clinical outcome, and provides therapeutic options.
- Authors: Stumpel DJ, Schneider P, van Roon EH, Boer JM, de Lorenzo P, Valsecchi MG, de Menezes RX, Pieters R, Stam RW
- Issue date: 2009 Dec 24
- Epigenetic landscape correlates with genetic subtype but does not predict outcome in childhood acute lymphoblastic leukemia.
- Authors: Gabriel AS, Lafta FM, Schwalbe EC, Nakjang S, Cockell SJ, Iliasova A, Enshaei A, Schwab C, Rand V, Clifford SC, Kinsey SE, Mitchell CD, Vora A, Harrison CJ, Moorman AV, Strathdee G
- Issue date: 2015
- Presence of clone-specific markers at birth in children with acute lymphoblastic leukaemia.
- Authors: Hjalgrim LL, Madsen HO, Melbye M, Jørgensen P, Christiansen M, Andersen MT, Pallisgaard N, Hokland P, Clausen N, Ryder LP, Schmiegelow K, Hjalgrim H
- Issue date: 2002 Oct 21
- Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia.
- Authors: Nordlund J, Bäcklin CL, Wahlberg P, Busche S, Berglund EC, Eloranta ML, Flaegstad T, Forestier E, Frost BM, Harila-Saari A, Heyman M, Jónsson OG, Larsson R, Palle J, Rönnblom L, Schmiegelow K, Sinnett D, Söderhäll S, Pastinen T, Gustafsson MG, Lönnerholm G, Syvänen AC
- Issue date: 2013 Sep 24