New therapy for rare leukemias

Researchers from the University of Helsinki, HUS Comprehensive Cancer Center and the University of Copenhagen have identified a potential new targeted therapy option for treating two rare subtypes (erythroid or megakaryoblastic)of acute myeloid leukemia using BCL-XL protein inhibitors. This could potentially improve patient outcomes if proven successful in clinical trials, states the university in a press release.

Leukemia is a type of cancer that affects the blood cells. It occurs when the body produces too many immature white blood cells, which crowd out the red blood cells and platelets that are essential for the body to function. Leukemia can be divided into four main categories – acute lymphoblastic leukemia (ALL), chronic lymphoblastic leukemia (CLL), acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). AML is the most common type of acute leukemia in adults.

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Currently, few treatment options are available to patients with erythroid or megakaryoblastic leukemias, two rare subtypes of the disease that are difficult to treat. This is due to the malignant cells resembling blood stem cells that produce red blood cells or platelets.

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Venetoclax

Venetoclax is a new targeted therapy option for the treatment of acute myeloid leukemia (AML). Venetoclax works by sensitising cancer cells to programmed cell death. However, a new study now shows that venetoclax does not appear to be effective against erythroid and megakaryoblastic leukemias.

In the laboratory, the researchers screened a wide selection of pharmaceutical agents that could be effective specifically against erythroid or megakaryoblastic leukemia cells. Among the more than 500 agents analysed, BCL-XL protein inhibitors in particular were effective in killing cancer cells isolated from these types of leukemia.

BCL-XL proteins have a similar function as BCL-2, which is the target of venetoclax. At the moment, BCL-XL inhibitors are not used to treat patients, but their efficacy and safety are currently being investigated in clinical trials.

“The introduction of venetoclax has significantly improved the prognosis of AML patients. However, our research indicates that venetoclax is unlikely to function optimally against the subtypes of AML in our focus,” said physician-scientist Olli Dufva.

Potential benefits

The laboratory findings provide evidence that patients with erythroid or megakaryoblastic acute leukemia would be a promising group for investigating the efficacy of BCL-XL inhibitors in clinical use,” said postdoctoral researcher Heikki Kuusanmäki.

“This finding may in the future improve the prognosis of these very rare and difficult-to-treat leukemias,” said Professor of Translational Haematology Satu Mustjoki from the University of Helsinki and HUS Comprehensive Cancer Center.