Innovative Drug Therapy Shows Promise for Acute Myeloid Leukemia Patients

A groundbreaking dual-drug therapy offers renewed hope for patients suffering from acute myeloid leukemia (AML), a particularly aggressive form of blood cancer. This innovative combination therapy, developed by researchers from Ludwig Cancer Research and other institutions, targets the underlying issue of impaired cell differentiation that characterizes AML, paving the way for potentially safer and more effective treatment options. Published in the prestigious journal *Nature* on June 8, 2025, the study articulates how the new approach could enhance survival rates and reduce toxicity compared to traditional chemotherapy.

Acute myeloid leukemia remains one of the most challenging blood cancers, with approximately 44,000 diagnoses occurring each year in the United States and Europe. The average survival time after diagnosis stands at a mere 8.5 months, largely due to the disease's rapid progression and its ability to hinder the maturation of young blood cells, known as myeloid progenitors. These immature cells accumulate in the bone marrow, disrupting the essential process of hematopoiesis, which is critical for healthy blood production and immune function.

Dr. Yang Shi, a prominent researcher and one of the study leaders at Ludwig Cancer Research, emphasized the significance of this new therapy, stating, “Impaired differentiation is a hallmark of myeloid cancers. The drug combination we have identified works by activating genes that drive cell differentiation while suppressing those that promote cancer growth.” This innovative approach draws inspiration from the successful treatment of acute promyelocytic leukemia (APL), where a similar tactic using the drugs ATRA and arsenic trioxide has achieved a remarkable cure rate of around 95%.

In developing this new therapy, the research team sought to replicate the success seen in APL treatments while addressing the broader spectrum of AML subtypes. The combination therapy utilizes two key inhibitors: GSK–LSD1 and LY2090314. The LSD1 inhibitor serves to block an enzyme that maintains the stem-like state of AML cells, while the GSK3 inhibitor, already under evaluation in cancer trials, complements the treatment by enabling the use of a lower and safer dose of the LSD1 inhibitor. This dual-targeting strategy demonstrates efficacy across multiple AML subtypes, as laboratory experiments reveal that the drug combination prompts leukemia cells to mature and halts their proliferation.

The therapy not only slows the progression of the disease but also appears to spare healthy blood cells, potentially minimizing side effects commonly associated with traditional chemotherapy. In mouse models implanted with human AML cells, the treatment extended survival and altered gene expression patterns in leukemia cells, aligning with those seen in patients who achieve better outcomes. Dr. Amir Hosseini, co-lead author of the study, noted, “We are also encouraged by the observation that the gene expression signature induced in leukemic cells by this combination therapy correlates with that observed in the cancer cells of AML patients who live relatively longer.”

While the concept of aiding cancer cell differentiation is not unprecedented, the focused dual targeting of LSD1 and GSK3 signifies a promising advancement in AML treatment strategies. This reprogramming of cancer cells at the genetic level could remove their stem-like characteristics, instead steering them toward normal cellular behavior. Notably, the therapy did not adversely affect healthy bone marrow cells, emphasizing its potential safety for human patients.

Patients with AML who are not candidates for stem cell transplants generally rely on conventional chemotherapy or targeted therapies like venetoclax, which still yield low survival rates for many. This innovative approach, centered on restoring balance rather than annihilating cells, could present an alternative pathway for treatment. Dr. Shi concluded, “Our findings provide compelling evidence to support the testing of this combination therapy in AML patients. Both of the inhibitors involved are not only available but have already been developed for human use and are currently being evaluated in clinical trials.”

Furthermore, the implications of this therapy may extend beyond AML, as the WNT pathway targeted in this treatment is implicated in various cancers. As research progresses, scientists remain optimistic that this once-overlooked strategy of fostering cancer cell maturation could emerge as a potent weapon in the broader fight against leukemia and potentially other aggressive tumors.