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| Status |
Public on Sep 15, 2021 |
| Title |
Targeting miR-126 in inv(16) acute myeloid leukemia inhibits leukemia development and leukemia stem cell maintenance |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Acute myeloid leukemia (AML) harboring inv(16)(p13q22) expresses high levels of miR-126. Here we show that the CBFB-MYH11 (CM) fusion gene upregulates miR-126 expression through aberrant miR-126 transcription and perturbed miR-126 biogenesis via the HDAC8/RAN-XPO5-RCC1 axis. Aberrant miR-126 upregulation promotes survival of leukemia-initiating progenitors and is critical for initiating and maintaining CM-driven AML. We show that miR-126 enhances MYC activity through the SPRED1/PLK2-ERK-MYC axis. Notably, genetic deletion of miR-126 significantly reduced AML rate and extended survival in CM knock-in mice. Therapeutic depletion of miR-126 with an anti-miR-126 (miRisten) inhibited AML cell survival, reduced leukemia burden and leukemia stem cell (LSC) activity in inv(16) AML murine and xenograft models. Combination of miRisten with chemotherapy further enhanced the anti-leukemia and anti-LSC activity. Overall, this study provides molecular insights for the mechanism and impact of miR-126 dysregulation in leukemogenesis and highlights the potential of miR-126 depletion as a new therapeutic approach for inv(16) AML.
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| Overall design |
Total 10 LSK samples were analyzed in this study. 5 samples as CM, 5 samples as CM/miR-126Δ/Δ
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| |
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| Contributor(s) |
Zhang L, Wu D, Li M, Li S, Chen W |
| Citation(s) |
34686664 |
| Submission date |
Sep 13, 2021 |
| Last update date |
Dec 02, 2021 |
| Contact name |
wei chen |
| E-mail(s) |
weichen2@coh.org
|
| Organization name |
City of Hope National Medical Center
|
| Department |
Cancer Biology-BRI
|
| Street address |
1500 E Duarte Rd
|
| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA762718 |
| SRA |
SRP336810 |
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