New Research Identifies Safe Target for Acute Myeloid Leukemia Treatment

Researchers at the Josep Carreras Leukaemia Research Institute have discovered a new target for treating acute myeloid leukemia (AML) that may pave the way for safer therapeutic options. The study, led by Dr. Marcus Buschbeck and Dr. René Winkler, focuses on a specific group of histones known as macroH2A. Their findings suggest that removing certain proteins from this family is tolerated well in experimental settings, particularly in mice.

The urgency for new treatments in AML is underscored by the high relapse rates associated with current therapies. Although existing treatments can temporarily control the disease, many patients experience severe relapses, necessitating novel approaches. The research team at the Josep Carreras Institute is committed to identifying druggable targets in blood cancers, particularly those related to chromatin—the structure that organizes genetic information within cells.

Histones play a critical role in maintaining chromatin structure and genome stability. Given that specific mutations in histones are linked to blood cancers, they represent potential therapeutic targets. Historically, targeting histones has been challenging due to their essential role in cell survival. Many proposed treatments were deemed too risky due to the potential for severe side effects. According to Ari Melnick, Director of the Josep Carreras Institute, this has hindered the development of new medicines aimed at this crucial mechanism in blood cancers.

In this recent study, Dr. Buschbeck’s team identified macroH2A as a subgroup of histones that could serve as viable therapeutic candidates. Previous research indicated a connection between macroH2A and AML, prompting further investigation. The team’s experiments, published in the journal Science Advances, assessed the effects of removing each of the three macroH2A variants in healthy mice. This research represents a significant step toward determining the suitability of these variants as drug targets for leukemia patients.

Collaboration with experts from the Helmholtz Center Munich and the German Mouse Clinic enhanced the study’s rigor. The facilities provided comprehensive monitoring capabilities, allowing researchers to track over 500 parameters in mice to detect any potential effects of the treatments. Surprisingly, the results indicated that the removal of macroH2A variants had minimal adverse effects on the mice’s health.

The most notable finding was a mild kidney condition observed after the removal of the macroH2A1.1 variant. This condition was attributed to a metabolic shift, where the mice altered their metabolism from fat to sugar. Fortunately, the researchers were able to mitigate this issue through simple dietary adjustments, ensuring the health of the animals was not compromised.

Overall, the research team concluded that targeting macroH2A histone variants presents a promising avenue for future AML treatments. This groundbreaking work has led to the establishment of a new research initiative at the Josep Carreras Leukaemia Research Institute, in conjunction with its international partners, to explore macroH2A variants as potential drug targets across various blood cancers.

The implications of this research are significant, as they open new pathways for developing more effective and safer treatments for patients suffering from acute myeloid leukemia and potentially other blood cancers. As the field progresses, the hope is to translate these findings into innovative therapies that can improve patient outcomes in the fight against these challenging diseases.