General Information
- Project ID
- OEP004818
- Project Name
- Targeting UHRF1-SAP30-MXD4 axis for leukemia initiating cell eradication in myeloid leukemia
- Description
- Aberrant self-renewal of leukemia initiation cells (LICs) drives aggressive acute myeloid leukemia (AML). Here, we report that UHRF1, an epigenetic regulator that recruits DNMT1 to methylate DNA, is highly expressed in AML and predicts poor prognosis. UHRF1 is required for myeloid leukemogenesis by maintaining self-renewal of LICs. Mechanistically, UHRF1 directly interacts with Sin3A associated protein 30 (SAP30) through two amino acids, G572 and F573 in its SRA domain, to repress gene expression. Depletion of UHRF1 or SAP30 derepresses an important target gene, MXD4, which encodes a MYC antagonist, and leads to suppression of leukemogenesis. Knockdown of MXD4 can rescue the leukemogenesis by activating the MYC pathway. Lastly, we identified a UHRF1 inhibitor, UF146, and demonstrated its significant therapeutic efficacy in the myeloid leukemia PDX model. Taken together, these studies reveal the mechanisms for altered epigenetic programs in AML and provide a promising targeted therapeutic strategy against AML.
- Publications
-
Targeting UHRF1-SAP30-MXD4 axis for leukemia initiating cell eradication in myeloid leukemia
Hu CL, Chen BY, Li Z, et al. Targeting UHRF1-SAP30-MXD4 axis for leukemia initiating cell eradication in myeloid leukemia. Cell Res. 2022;32(12):1105-1123. doi:10.1038/s41422-022-00735-6
(PMID: 36302855) (DOI: 10.1038/s41422-022-00735-6)
Project information
- Experiments
- 44
Experiment ID Experiment name Experiment type Create Date OEX026042 Kasumi-1_DMSO-1_2.fastq.gz Transcriptomic 2023-12-11 OEX026043 Kasumi-1_DMSO-2_1.fastq.gz Transcriptomic 2023-12-11 OEX026044 Kasumi-1_DMSO-1_1.fastq.gz Transcriptomic 2023-12-11 OEX026045 Kasumi-1_DMSO-2_2.fastq.gz Transcriptomic 2023-12-11 OEX026046 Kasumi-1_IgG_1.fastq.gz Transcriptomic 2023-12-11 OEX026047 Kasumi-1_shCtrl-1_1.fastq.gz Transcriptomic 2023-12-11 OEX026048 Kasumi-1_IgG_2.fastq.gz Transcriptomic 2023-12-11 OEX026049 Kasumi-1_shCtrl-1_2.fastq.gz Transcriptomic 2023-12-11 OEX026050 Kasumi-1_shCtrl-2_2.fastq.gz Transcriptomic 2023-12-11 OEX026051 Kasumi-1_shCtrl-2_1.fastq.gz Transcriptomic 2023-12-11 OEX026052 Kasumi-1_shUHRF1-1_1.fastq.gz Transcriptomic 2023-12-11 OEX026053 Kasumi-1_shUHRF1-1_2.fastq.gz Transcriptomic 2023-12-11 OEX026054 Kasumi-1_shUHRF1-2_1.fastq.gz Transcriptomic 2023-12-11 OEX026055 Kasumi-1_UF146-1_1.fastq.gz Transcriptomic 2023-12-11 OEX026056 Kasumi-1_UF146-1_2.fastq.gz Transcriptomic 2023-12-11 OEX026057 Kasumi-1_shUHRF1-2_2.fastq.gz Transcriptomic 2023-12-11 OEX026058 Kasumi-1_UF146-2_1.fastq.gz Transcriptomic 2023-12-11 OEX026059 THP-1_DMSO-1_1.fastq.gz Transcriptomic 2023-12-11 OEX026060 Kasumi-1_UF146-2_2.fastq.gz Transcriptomic 2023-12-11 OEX026061 THP-1_DMSO-1_2.fastq.gz Transcriptomic 2023-12-11 OEX026062 THP-1_DMSO-2_1.fastq.gz Transcriptomic 2023-12-11 OEX026063 THP-1_DMSO-2_2.fastq.gz Transcriptomic 2023-12-11 OEX026064 THP-1_shCtrl-1_1.fastq.gz Transcriptomic 2023-12-11 OEX026065 THP-1_IgG_1.fastq.gz Transcriptomic 2023-12-11 OEX026066 THP-1_IgG_2.fastq.gz Transcriptomic 2023-12-11 OEX026067 THP-1_shCtrl-1_2.fastq.gz Transcriptomic 2023-12-11 OEX026068 THP-1_shCtrl-2_2.fastq.gz Transcriptomic 2023-12-11 OEX026069 THP-1_shCtrl-2_1.fastq.gz Transcriptomic 2023-12-11 OEX026070 THP-1_shUHRF1-1_1.fastq.gz Transcriptomic 2023-12-11 OEX026071 THP-1_shUHRF1-1_2.fastq.gz Transcriptomic 2023-12-11 OEX026072 THP-1_shUHRF1-2_2.fastq.gz Transcriptomic 2023-12-11 OEX026073 THP-1_shUHRF1-2_1.fastq.gz Transcriptomic 2023-12-11 OEX026074 THP-1_UF146-2_1.fastq.gz Transcriptomic 2023-12-11 OEX026075 THP-1_UF146-1_1.fastq.gz Transcriptomic 2023-12-11 OEX026076 THP-1_UF146-1_2.fastq.gz Transcriptomic 2023-12-11 OEX026077 THP-1_UF146-2_2.fastq.gz Transcriptomic 2023-12-11 OEX026078 Kasumi-1_SAP30_CUT_TAG_1.fastq.gz Transcriptomic 2023-12-11 OEX026079 Kasumi-1_SAP30_CUT_TAG_2.fastq.gz Transcriptomic 2023-12-11 OEX026080 Kasumi-1_UHRF1_CUT_TAG_1.fastq.gz Transcriptomic 2023-12-11 OEX026081 THP-1_SAP30_CUT_TAG_1.fastq.gz Transcriptomic 2023-12-11 OEX026082 THP-1_SAP30_CUT_TAG_2.fastq.gz Transcriptomic 2023-12-11 OEX026083 Kasumi-1_UHRF1_CUT_TAG_2.fastq.gz Transcriptomic 2023-12-11 OEX026084 THP-1_UHRF1_CUT_TAG_2.fastq.gz Transcriptomic 2023-12-11 OEX026085 THP-1_UHRF1_CUT_TAG_1.fastq.gz Transcriptomic 2023-12-11 - Samples
- 44
Sample ID Sample Name Sample Subject Type Organism Tissue Create Date OES340469 Kasumi-1_DMSO-1_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340470 Kasumi-1_DMSO-2_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340471 Kasumi-1_DMSO-1_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340472 Kasumi-1_DMSO-2_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340473 Kasumi-1_IgG_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340474 Kasumi-1_shCtrl-1_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340475 Kasumi-1_IgG_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340476 Kasumi-1_shCtrl-1_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340477 Kasumi-1_shCtrl-2_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340478 Kasumi-1_shCtrl-2_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340479 Kasumi-1_shUHRF1-1_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340480 Kasumi-1_shUHRF1-1_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340481 Kasumi-1_shUHRF1-2_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340482 Kasumi-1_UF146-1_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340483 Kasumi-1_UF146-1_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340484 Kasumi-1_shUHRF1-2_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340485 Kasumi-1_UF146-2_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340486 THP-1_DMSO-1_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340487 Kasumi-1_UF146-2_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340488 THP-1_DMSO-1_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340489 THP-1_DMSO-2_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340490 THP-1_DMSO-2_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340491 THP-1_shCtrl-1_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340492 THP-1_IgG_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340493 THP-1_IgG_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340494 THP-1_shCtrl-1_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340495 THP-1_shCtrl-2_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340496 THP-1_shCtrl-2_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340497 THP-1_shUHRF1-1_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340498 THP-1_shUHRF1-1_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340499 THP-1_shUHRF1-2_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340500 THP-1_shUHRF1-2_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340501 THP-1_UF146-2_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340502 THP-1_UF146-1_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340503 THP-1_UF146-1_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340504 THP-1_UF146-2_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340505 Kasumi-1_SAP30_CUT_TAG_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340506 Kasumi-1_SAP30_CUT_TAG_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340507 Kasumi-1_UHRF1_CUT_TAG_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340508 THP-1_SAP30_CUT_TAG_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340509 THP-1_SAP30_CUT_TAG_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340510 Kasumi-1_UHRF1_CUT_TAG_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340511 THP-1_UHRF1_CUT_TAG_2.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 OES340512 THP-1_UHRF1_CUT_TAG_1.fastq.gz Cell line Homo sapiens Myeloblast 2023-12-11 - Runs
-
44
Run ID Run Name Experiment Sample Data Num Create Date OER447577 Kasumi-1_DMSO-1_2.fastq.gz OEX026042 OES340469 1 2023-12-11 OER447578 Kasumi-1_DMSO-2_1.fastq.gz OEX026043 OES340470 1 2023-12-11 OER447579 Kasumi-1_DMSO-1_1.fastq.gz OEX026044 OES340471 1 2023-12-11 OER447580 Kasumi-1_DMSO-2_2.fastq.gz OEX026045 OES340472 1 2023-12-11 OER447581 Kasumi-1_IgG_1.fastq.gz OEX026046 OES340473 1 2023-12-11 OER447582 Kasumi-1_shCtrl-1_1.fastq.gz OEX026047 OES340474 1 2023-12-11 OER447583 Kasumi-1_IgG_2.fastq.gz OEX026048 OES340475 1 2023-12-11 OER447584 Kasumi-1_shCtrl-1_2.fastq.gz OEX026049 OES340476 1 2023-12-11 OER447585 Kasumi-1_shCtrl-2_2.fastq.gz OEX026050 OES340477 1 2023-12-11 OER447586 Kasumi-1_shCtrl-2_1.fastq.gz OEX026051 OES340478 1 2023-12-11 OER447587 Kasumi-1_shUHRF1-1_1.fastq.gz OEX026052 OES340479 1 2023-12-11 OER447588 Kasumi-1_shUHRF1-1_2.fastq.gz OEX026053 OES340480 1 2023-12-11 OER447589 Kasumi-1_shUHRF1-2_1.fastq.gz OEX026054 OES340481 1 2023-12-11 OER447590 Kasumi-1_UF146-1_1.fastq.gz OEX026055 OES340482 1 2023-12-11 OER447591 Kasumi-1_UF146-1_2.fastq.gz OEX026056 OES340483 1 2023-12-11 OER447592 Kasumi-1_shUHRF1-2_2.fastq.gz OEX026057 OES340484 1 2023-12-11 OER447593 Kasumi-1_UF146-2_1.fastq.gz OEX026058 OES340485 1 2023-12-11 OER447594 THP-1_DMSO-1_1.fastq.gz OEX026059 OES340486 1 2023-12-11 OER447595 Kasumi-1_UF146-2_2.fastq.gz OEX026060 OES340487 1 2023-12-11 OER447596 THP-1_DMSO-1_2.fastq.gz OEX026061 OES340488 1 2023-12-11 OER447597 THP-1_DMSO-2_1.fastq.gz OEX026062 OES340489 1 2023-12-11 OER447598 THP-1_DMSO-2_2.fastq.gz OEX026063 OES340490 1 2023-12-11 OER447599 THP-1_shCtrl-1_1.fastq.gz OEX026064 OES340491 1 2023-12-11 OER447600 THP-1_IgG_1.fastq.gz OEX026065 OES340492 1 2023-12-11 OER447601 THP-1_IgG_2.fastq.gz OEX026066 OES340493 1 2023-12-11 OER447602 THP-1_shCtrl-1_2.fastq.gz OEX026067 OES340494 1 2023-12-11 OER447603 THP-1_shCtrl-2_2.fastq.gz OEX026068 OES340495 1 2023-12-11 OER447604 THP-1_shCtrl-2_1.fastq.gz OEX026069 OES340496 1 2023-12-11 OER447605 THP-1_shUHRF1-1_1.fastq.gz OEX026070 OES340497 1 2023-12-11 OER447606 THP-1_shUHRF1-1_2.fastq.gz OEX026071 OES340498 1 2023-12-11 OER447607 THP-1_shUHRF1-2_2.fastq.gz OEX026072 OES340499 1 2023-12-11 OER447608 THP-1_shUHRF1-2_1.fastq.gz OEX026073 OES340500 1 2023-12-11 OER447609 THP-1_UF146-2_1.fastq.gz OEX026074 OES340501 1 2023-12-11 OER447610 THP-1_UF146-1_1.fastq.gz OEX026075 OES340502 1 2023-12-11 OER447611 THP-1_UF146-1_2.fastq.gz OEX026076 OES340503 1 2023-12-11 OER447612 THP-1_UF146-2_2.fastq.gz OEX026077 OES340504 1 2023-12-11 OER447613 Kasumi-1_SAP30_CUT_TAG_1.fastq.gz OEX026078 OES340505 1 2023-12-11 OER447614 Kasumi-1_SAP30_CUT_TAG_2.fastq.gz OEX026079 OES340506 1 2023-12-11 OER447615 Kasumi-1_UHRF1_CUT_TAG_1.fastq.gz OEX026080 OES340507 1 2023-12-11 OER447616 THP-1_SAP30_CUT_TAG_1.fastq.gz OEX026081 OES340508 1 2023-12-11 OER447617 THP-1_SAP30_CUT_TAG_2.fastq.gz OEX026082 OES340509 1 2023-12-11 OER447618 Kasumi-1_UHRF1_CUT_TAG_2.fastq.gz OEX026083 OES340510 1 2023-12-11 OER447619 THP-1_UHRF1_CUT_TAG_2.fastq.gz OEX026084 OES340511 1 2023-12-11 OER447620 THP-1_UHRF1_CUT_TAG_1.fastq.gz OEX026085 OES340512 1 2023-12-11
Author Information
- Create Date
- 2023-12-11
- Last Modified
- 2024-02-05
- Submission
- Wang lan
- Shanghai Institute of Nutrition and Health