Large-scale analysis of DNA methylation in chronic lymphocytic leukemia.
OBJECTIVE
B-cell chronic lymphocytic leukemia (CLL) is a heterogeneous malignancy that clinically ranges from indolent to rapidly progressive. CLL, like other cancers, can be affected by epigenetic alterations.


METHODS
A microarray discovery-based study was initiated to determine DNA methylation in CLL cases with a range of CD38 expression (1–92%).


RESULTS
Many loci were either methylated or unmethylated across all CD38 levels, but differential methylation was also observed for some genes. Genomic sequencing of DLEU7 confirmed extensive cytosine methylation preferentially in patient samples with low CD38 expression, whereas NRP2, SFRP2 and ADAM12 were more commonly methylated in those with high CD38 expression.


CONCLUSIONS
This study demonstrates that CLL is affected by CpG island methylation in some genes that segregate with CD38 expression levels, while most others show similar methylation patterns across all levels. The CpG island methylation in certain functional gene groups and pathway-associated genes that are known to be deregulated in CLL provides additional insights into the CLL methylome and epigenetic contribution to cellular dysfunction. It will now be useful to investigate the effectiveness of epigenetic therapeutic reversal of these alterations to develop effective treatments for the disease.
Rahmatpanah
Farahnaz B
FB
Department of Pathology and Anatomical Sciences, Ellis Fischel Cancer Center, University of Missouri School of Medicine, Columbia, Missouri 65212, USA.
Carstens
Stephanie
S
Hooshmand
Sam I
SI
Welsh
Elise C
EC
Sjahputera
Ozy
O
Taylor
Kristen H
KH
Bennett
Lynda B
LB
Shi
Huidong
H
Davis
J Wade
JW
Arthur
Gerald L
GL
Shanafelt
Tait D
TD
Kay
Neil E
NE
Wooldridge
James E
JE
Caldwell
Charles W
CW
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000072199:ADAM12 Protein; D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018899:CpG Islands; D004247:DNA / Q000032:analysis*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D056426:Genetic Loci; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
D051722:ADAM Proteins; D000072199:ADAM12 Protein; D051997:ADP-ribosyl Cyclase 1; D004247:DNA; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D039943:Neuropilin-2; D025521:Tumor Suppressor Proteins; C482307:DLEU7 protein, human; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C000606480:ADAM12 protein, human