The protein menin, already known as a target for some forms of leukemia, may also hold promise for treating myeloproliferative neoplasms (MPNs). Researchers at St. Jude Children’s Research Hospital found that inhibiting menin significantly extended survival and reversed multiple disease features in preclinical models of MPNs. The findings were published in Cancer Cell.

Key Takeaways

  • MPNs are a group of blood cancers that include myelofibrosis, polycythemia vera, and essential thrombocythemia.
  • Menin is a protein that supports the growth of cancerous blood cells and has already been targeted in clinical trials for acute leukemias.
  • In the new study, blocking menin with experimental inhibitors improved survival and reduced fibrosis, inflammation, and abnormal blood cell counts in animal models.
  • The findings provide the first preclinical evidence that menin inhibition could be a viable strategy for treating MPNs.

What Are Myeloproliferative Neoplasms?

Myeloproliferative neoplasms are rare, chronic blood cancers in which the bone marrow produces too many red blood cells, white blood cells, or platelets. The three main subtypes are polycythemia vera (too many red blood cells), essential thrombocythemia (too many platelets), and myelofibrosis (scarring of the bone marrow). Many patients eventually develop acute leukemia, and current treatments often cannot prevent disease progression. There is a high unmet need for therapies that target the underlying drivers of MPNs.

The Role of Menin in MPNs

Menin is a scaffold protein that interacts with various transcription factors to regulate gene expression. In certain leukemias, menin acts as a cofactor for proteins that drive cancer growth. Previous work has led to the development of oral menin inhibitors that are now being tested in clinical trials for acute myeloid leukemia. The St. Jude team suspected that menin might also be important in MPNs because the same genetic pathways, particularly those involving the protein MLL, are active in both diseases.

Using mouse models of MPN, the researchers tested two different menin inhibitors. They found that blocking menin not only extended survival but also reversed several hallmarks of disease: it reduced bone marrow fibrosis, normalized blood cell counts, and lowered levels of inflammatory cytokines. Importantly, the treatment also decreased the number of mutant stem cells that drive the disease, suggesting a potential for lasting benefit.

Implications for Future Treatment

The study provides a strong rationale for testing menin inhibitors in patients with MPNs, particularly those who have not responded to other therapies or who are at high risk of leukemic transformation. Because menin inhibitors are already in clinical trials for leukemia, the safety profiles and dosing schedules for these drugs are partly known, which could accelerate their evaluation for MPNs. However, the researchers caution that more work is needed to understand which patient subgroups might benefit most and whether combining menin inhibitors with other drugs could enhance the response.

Frequently Asked Questions

What is menin and why is it a target?

Menin is a protein that helps regulate gene expression. In certain blood cancers, it interacts with cancer-driving proteins to keep malignant cells alive and proliferating. Inhibiting menin disrupts these interactions, causing cancer cells to die or differentiate.

How was the study conducted?

The St. Jude researchers used genetically engineered mouse models that develop MPN-like disease, along with cell lines and primary patient samples. They treated these models with two different menin inhibitors and monitored survival, blood counts, bone marrow fibrosis, and stem cell numbers.

When might menin inhibitors be available for MPN patients?

Menin inhibitors have not yet been tested in clinical trials for MPNs. The ongoing trials in acute leukemia will provide safety and dosing data that could help design MPN-specific studies. If future trials show efficacy and safety, menin inhibitors could become an option within several years, but that timeline remains uncertain.

This is an original report by Vital Signs Today, informed by reporting from Medical Xpress. Read the original source.

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