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| Status |
Public on Jul 19, 2019 |
| Title |
Downregulation of the histone methyltransferase SETD2 promotes imatinib resistance in chronic myeloid leukemia cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Epigenetic modifiers were important players in the development of hematological malignancies and sensitivity to therapy. Mutations of SET domain-containing 2 (SETD2), a methyltransferase that catalyzes the trimethylation of histone 3 on lysine 36 (H3K36me3), were found in various myeloid malignancies. However, the detailed mechanisms through which SETD2 confers chronic myeloid leukemia progression and resistance to therapy targeting on BCR-ABL remain unclear. Here we found SETD2 acted as a tumor suppressor in CML. The novel oncogenic targets MYCN and ERG were shown to be the direct downstream targets of SETD2, where their overexpression induced by SETD2 knockdown caused imatinib insensitivity and leukemic stem cell enrichment in CML cell lines. Treatment with JIB-04, an inhibitor that restores H3K36me3 levels through blockade of its demethylation, successfully improved the cell’s imatinib sensitivity and enhanced the chemotherapeutic effect.
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| |
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| Overall design |
RNA Sequencing Analysis between Imatinib Sensitive and Resistant TF1-BCR-ABL Cells.
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| |
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| Contributor(s) |
Sheng Y |
| Citation(s) |
31054182 |
| Submission date |
Jan 10, 2019 |
| Last update date |
Jul 19, 2019 |
| Contact name |
Sheng Yaru |
| E-mail(s) |
shengyaru@sjtu.edu.cn
|
| Organization name |
State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center
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| Street address |
Stem Cell Research Center, Ren Ji Hospital, 160 Pujian Road
|
| City |
Shanghai |
| ZIP/Postal code |
200127 |
| Country |
China |
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| Platforms (1) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA514230 |
| SRA |
SRP178217 |
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