Abstract
Aims: 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. Materials & 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. Conclusion: 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 39-61 |
| Number of pages | 23 |
| Journal | Epigenomics |
| Volume | 1 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 2009 |
| Externally published | Yes |
Fingerprint
Keywords
- CD38 expression
- CLL
- DNA methylation
- Epigenetics
- Leukemia
ASJC Scopus subject areas
- Genetics
- Cancer Research
Cite this
Large-scale analysis of DNA methylation in chronic lymphocytic leukemia. / Rahmatpanah, Farahnaz B.; Carstens, Stephanie; Hooshmand, Sam I.; Welsh, Elise C.; Sjahputera, Ozy; Taylor, Kristen H.; Bennett, Lynda B.; Shi, Huidong; Davis, J. Wade; Arthur, Gerald L.; Shanafelt, Tait D.; Kay, Neil Elliot; Wooldridge, James E.; Caldwell, Charles W.
In: Epigenomics, Vol. 1, No. 1, 10.2009, p. 39-61.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Large-scale analysis of DNA methylation in chronic lymphocytic leukemia
AU - Rahmatpanah, Farahnaz B.
AU - Carstens, Stephanie
AU - Hooshmand, Sam I.
AU - Welsh, Elise C.
AU - Sjahputera, Ozy
AU - Taylor, Kristen H.
AU - Bennett, Lynda B.
AU - Shi, Huidong
AU - Davis, J. Wade
AU - Arthur, Gerald L.
AU - Shanafelt, Tait D.
AU - Kay, Neil Elliot
AU - Wooldridge, James E.
AU - Caldwell, Charles W.
PY - 2009/10
Y1 - 2009/10
N2 - Aims: 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. Materials & 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. Conclusion: 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.
AB - Aims: 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. Materials & 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. Conclusion: 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.
KW - CD38 expression
KW - CLL
KW - DNA methylation
KW - Epigenetics
KW - Leukemia
UR - http://www.scopus.com/inward/record.url?scp=77954126563&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954126563&partnerID=8YFLogxK
U2 - 10.2217/epi.09.10
DO - 10.2217/epi.09.10
M3 - Article
VL - 1
SP - 39
EP - 61
JO - Epigenomics
JF - Epigenomics
SN - 1750-1911
IS - 1
ER -