Researchers from the University of Helsinki, the HUS Comprehensive Cancer Center and the University of Copenhagen have developed a potential new targeted therapy option for the treatment of two rare subtypes (erythroid or megakaryoblastic) of acute myeloid leukemia using BCL-XL protein inhibitors. This could potentially improve outcomes for patients if success is demonstrated in clinical trials, the university said 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 form of acute leukemia in adults. Currently, there are few treatment options for patients with erythroid or megakaryoblastic leukemia, two rare subtypes of the disease that are difficult to treat. This is because the malignant cells resemble blood stem cells that produce red blood cells or platelets.
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Venetoclax
Venetoclax is a new targeted therapy for the treatment of acute myeloid leukemia (AML). Venetoclax works by sensitizing cancer cells to programmed cell death. However, a new study now shows that venetoclax appears to be ineffective against erythroid and megakaryoblastic leukemias. In the laboratory, the researchers examined a wide selection of pharmaceutical agents that could be specifically active against erythroid or megakaryoblastic leukemia cells.
Of the more than 500 agents studied, BCL-XL protein inhibitors were particularly effective in killing cancer cells isolated from these types of leukemia. BCL-XL proteins have a similar function to BCL-2, the target of venetoclax. Currently, 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 probably not optimally effective against the subtypes of AML that we are targeting,” said physician-researcher Olli Dufva.
Improve
The laboratory results provide evidence that patients with erythroid or megakaryoblastic acute leukemia represent a promising group for investigating the efficacy of BCL-XL inhibitors in clinical use,” said postdoctoral researcher Heikki Kuusanmäki. “This finding may improve the prognosis of these very rare and difficult-to-treat leukemias in the future,” said Professor of Translational Hematology Satu Mustjoki from the University of Helsinki and the HUS Comprehensive Cancer Center.