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| Status |
Public on Dec 29, 2009 |
| Title |
Promoter hypermethylation in MLL-r leukemia: biology and therapeutic targeting |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
MLL-r infant acute lymphoblastic leukemia (ALL) has largely unclear oncogenesis. It has been shown unrelated to copy number change or mutations in the tyrosine kinome. We therefore, explored the possible role of genome wide CpG island hypermethylation in MLL-r infant ALL. We employed the HpaII-tiny fragment Enrichment by Ligation-mediated PCR (HELP) assay to examine MLL-r infant leukemia samples (n=5), other common childhood ALL (n=5) and normals (n=5). We then investigated biological correlation and the therapeutic potential of 5-aza-2’-deoxycytidine (decitabine). Analysis of the HELP assay showed both tight clustering of samples into their biological groups and that MLL-r infant leukemia was globally and comparatively hypermethylated. Further, a majority of genes chosen for analysis from the HELP assay were silenced or under-expressed. MLL-r cell lines showed dose and time-dependent cell kill when treated with decitabine and most down-regulated genes showed increase in expression. This was not seen in the MLL-wt cell line. For the re-expressed genes, methylation specific PCR confirmed preferential promoter methylation in MLL-r samples. Together, this suggests that methylation signatures are unique in pediatric ALL, that promoter hypermethylation may play a significant role in MLL-r infant leukemogenesis, that this can be reversed and demethylating agents may be a potential new therapeutic option in infant leukemia.
Keywords: DNA methylation profiling
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| Overall design |
Direct comparison of DNA methylation in leukemic blasts from 5 infants with MLL-r ALL with 5 children with other common types of ALL and 5 normal samples consisting of CD34+ selected cord blood cells (n=3) and CD19+ selected cord blood cells (n=2)
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| Contributor(s) |
Schafer ES, Figueroa ME, Melnick A, Brown P |
| Citation(s) |
20215641 |
| Submission date |
Dec 28, 2009 |
| Last update date |
Mar 21, 2012 |
| Contact name |
Eric Stephen Schafer |
| E-mail(s) |
eschafe1@jhmi.edu
|
| Phone |
(410) 955-8817
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| Fax |
(410) 955-8897
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| Organization name |
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
|
| Department |
Pediatrics and Oncology
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| Lab |
Patrick Brown Laboratory
|
| Street address |
CRB1, Room 252a, 1650 Orleans St.
|
| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21287 |
| Country |
USA |
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| Platforms (1) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA122493 |
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