Novel targeted therapy regimens show promise in aggressive AML subtype

MD Anderson Research News December 23, 2025

• MECOM-rearranged acute myeloid leukemia (AML) is an aggressive and hard-to-treat leukemia 

• Researchers combined three inhibitors and observed cancer cell death and increased survival in lab models 

Researchers at The University of Texas MD Anderson Cancer Center have identified new potential combination therapies to target high-risk MECOM-rearranged acute myeloid leukemia (AML) – a challenging subtype of the disease – according to new research published in Leukemia.  

The study was led by Christine Birdwell, Ph.D., research scientist; Warren Fiskus, Ph.D., associate  professor of Leukemia; and Kapil Bhalla, M.D., professor of Leukemia.  

“Patients with this aggressive and hard-to-treat leukemia have limited therapeutic options,” Fiskus said. “Our findings provide us with a promising pathway using a combination of therapies that has shown to reduce cancer cells and increase survival.”  

What did researchers investigate in this study on MECOM-rearranged AML?  

MECOM-rearranged AML is an aggressive blood cancer that forms when the MECOM gene becomes rearranged, causing excess production of the harmful protein EVI1and reduced levels of the GATA2 protein. Together, these changes help cancer cells grow quickly and resist treatment.  

The study examined why this aggressive leukemia subtype is resistant to standard therapies. Using a large, unbiased drug screen, the researchers discovered the MECOM-rearranged AML cancer cells rely heavily on several key pathways and proteins to survive.  

Based on these discoveries, researchers examined combinations of drugs that block key pathways used to target the cancer cells. The regimens included mivebresib, a BET inhibitor; dactolisib, a PI3K/mTOR inhibitor; and LCL161, an IAP inhibitor.  

What were the effects of these therapies on MECOM-rearranged AML?  

The study found each drug was more effective at selectively killing MECOM-rearranged AML cells than other types of AML cells. The drugs were effective in lowering levels of cancer-promoting proteins EVI1, c-Myc, and c-Myb.  

When the drugs were combined, there was a significant improvement in their efficacy at attacking and killing cancer cells. The combination triggered a strong response and significantly reduced cancer cells in lab models, increasing survival.  

These findings warrant further testing for potential development of new combination therapies, including triplet regimens for patients to overcome treatment resistance in MECOM-rearranged AML. 

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This research was supported by the National Institutes of Health/National Cancer Institute (5P30 CA016672-40, 1S10OD024977-01, P30 CA125123, P50 HD103555, S10 OD026804, R01 CA255721, P50 CA100632) and the Cancer Prevention and Research Institute of Texas. A full list of collaboration authors and their disclosures can be found with the paper in Leukemia.