Targeting epigenetic drivers in mixed-lineage (MLL-rearranged) leukemia
Combinational Targeting the Feed-forward Epigenetic Circuitry in Mixed Lineage Leukemia
['FUNDING_R37'] · MAYO CLINIC ROCHESTER · NIH-11299328
Testing whether blocking two epigenetic enzymes together can better stop MLL-rearranged acute leukemia in patients with this subtype.
Quick facts
| Phase | ['FUNDING_R37'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | MAYO CLINIC ROCHESTER (nih funded) |
| Locations | 1 site (ROCHESTER, UNITED STATES) |
| Trial ID | NIH-11299328 on ClinicalTrials.gov |
What this research studies
Researchers at Mayo Clinic are exploring a combination approach that targets DOT1L and the PHF20/KAT8 acetylation complex, two epigenetic mechanisms that keep leukemia-driving genes turned on in MLL-rearranged leukemia. The team will use laboratory models, cell lines (including human leukemia cells), and high-density CRISPR protein scanning to map functional elements that control oncogene activity. They will test whether combining DOT1L inhibitors with agents that disrupt PHF20/KAT8 reduces cancer gene expression and leukemia cell survival more than single agents. This preclinical work aims to guide future combination therapies for patients with this aggressive leukemia subtype.
Who could benefit from this research
Good fit: People with MLL-rearranged (MLL-r) acute leukemia, particularly those with relapsed or treatment-resistant disease, would be the eventual candidates for therapies informed by this research.
Not a fit: Patients with other leukemia subtypes or cancers driven by different genetic changes are unlikely to benefit from therapies targeting DOT1L/PHF20/KAT8.
Why it matters
Potential benefit: If successful, the work could point to new combination drug strategies that more effectively suppress oncogenes and lead to better treatments for MLL-rearranged leukemia.
How similar studies have performed: DOT1L inhibitors have produced some clinical responses as single agents in MLL-r leukemia, but combining DOT1L inhibition with PHF20/KAT8 targeting is a novel strategy not yet tested in patients.
Where this research is happening
ROCHESTER, UNITED STATES
- MAYO CLINIC ROCHESTER — ROCHESTER, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: CHEN, CHUN-WEI DAVID — MAYO CLINIC ROCHESTER
- Study coordinator: CHEN, CHUN-WEI DAVID
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions: Cancer Genes