Researchers screened small molecules and identified that the GSK3 inhibitor LY2090314 synergizes with the LSD1 inhibitor GSK–LSD1 to enhance differentiation of AML cells, as shown in a mouse model.

In laboratory tests with mouse leukemic cells, the drug combination successfully induced differentiation and extended survival in mice with human AML cells, selectively targeting leukemic cells while minimizing toxicity to healthy cells.

The differentiation block in AML presents a potential therapeutic target, as it prevents normal myeloid maturation and favors the self-renewal of leukemia cells.

The findings support further testing of this combination therapy in AML patients, as both drugs are already available and in clinical trials, which could pave the way for improved treatment options.

The gene expression changes induced by this combination therapy correlate with better survival outcomes in AML patients, suggesting its potential clinical relevance.

A recent study from Ludwig Cancer Research has proposed a novel treatment strategy for acute myelogenous leukemia (AML), a severe blood cancer with a median survival of only 8.5 months after diagnosis.

Approximately 44,000 new patients are diagnosed with AML annually in the USA and EU, highlighting the urgent need for innovative treatment options.

The study received support from various institutions, including the National Institutes of Health and Cancer Research UK, underscoring its significance in cancer research.

AML is characterized by the impaired differentiation of myeloid progenitor cells, leading to an accumulation of immature cells that disrupt normal blood cell production.

The study focuses on targeting dysfunctional gene expression in leukemic stem cells, particularly through the action of the epigenetic enzyme LSD1, which is highly expressed in AML.

Researchers, led by Yang Shi and Amir Hosseini, propose a combination therapy that activates differentiation-driving genes while inhibiting genes linked to cancer growth, addressing the differentiation block seen in AML.

The study explores the combination of LSD1 inhibitors and GSK3 inhibitors as a novel approach to induce AML cell differentiation, building on insights from successful treatments like ATRA and ATO in acute promyelocytic leukemia (APL).