| RRC ID |
18675
|
| 著者 |
Ikawa Y, Sugimoto N, Koizumi S, Yachie A, Saikawa Y.
|
| タイトル |
Dense methylation of types 1 and 2 regulatory regions of the CD10 gene promoter in infant acute lymphoblastic leukemia with MLL/AF4 fusion gene.
|
| ジャーナル |
J Pediatr Hematol Oncol
|
| Abstract |
SUMMARY:Infant acute lymphoblastic leukemia (ALL) displays distinct biologic and clinical features with a poor prognosis. The CD10-negative immunophenotype of infant ALL is a hallmark and provides a predictable signature of mixed-lineage leukemia (MLL) rearrangement. Although CD10 negativity reflects an earlier stage of B-cell development, complete IgH gene rearrangements (VDJH), found in almost half of the patients, show more mature IgH status. Discordance between immunophenotype and genotype of infant ALL suggests an aberrant process in immunophenotypic steps of differentiation or a secondary down-regulation of CD10 expression. In this study, CD10-negative infant ALL with MLL/AF4, CD10-positive infant ALL with germline MLL, CD10-positive pre-B ALL cell line, infant acute myeloid leukemia (AML; M5) with MLL/AF9 and pediatric AML (M2) with AML1/ETO were analyzed for VDJH status and methylation of CD10 gene promoters. Three of the 4 infant ALL samples showed complete rearrangements of the VDJH gene with productive joints. Bisulfite sequencing of CD10 type 1 and 2 promoters showed that more than 84% of the cytosine-phosphate-guanine (CpG) dinucleotides identified were methylated in all 3 CD10-negative infant ALL samples with MLL/AF4. The CpG dinucleotides distributed in the clusters of putative Sp1-binding sites and functionally active regulatory regions of the promoters were fully methylated. In contrast, none of the CpG dinucleotides were methylated in the CD10-positive ALL samples. Structural evidence of dense methylation in the CD10 gene promoter suggested that methylated transcription factor binding sites contribute to CD10 silencing as an epigenetic mechanism.
|
| 巻・号 |
32(1)
|
| ページ |
4-10
|
| 公開日 |
2010-1-1
|
| DOI |
10.1097/MPH.0b013e3181c29c3c
|
| PII |
00043426-201001000-00003
|
| PMID |
20051780
|
| MeSH |
Binding Sites
CpG Islands
DNA Methylation*
Gene Rearrangement
Genes, Immunoglobulin
Humans
Infant, Newborn
Myeloid-Lymphoid Leukemia Protein*
Neprilysin / genetics*
Oncogene Proteins, Fusion*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
Promoter Regions, Genetic
Regulatory Sequences, Nucleic Acid / genetics*
Sp1 Transcription Factor
|
| IF |
1.016
|
| 引用数 |
11
|
|
WOS 分野
|
PEDIATRICS
ONCOLOGY
HEMATOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HAL-01(RCB0540) |
