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University of Basel

16 September 2021

Improving leukemia therapy with targeted treatment approaches

blood smear
Blood smear with abnormal high platelet and white blood cell count. (Photo: iStock)

In chronic leukemias, blocking the overactive kinase JAK2 by a targeted therapy approach is only mitigating the patients’ symptoms, but cannot truly change the course of the disease. A study by the University of Basel has shown that it may be possible to improve the therapeutic effects by additionally inhibiting a specific signaling pathway. The results are so convincing that they are already being incorporated into clinical studies in a “bench-to-bedside” approach.

In myeloproliferative neoplasms, a form of chronic leukemia, the body constantly produces too many blood cells such as erythrocytes, platelets and granulocytes. This may lead to thrombosis, enlarged spleen and constitutional symptoms such as weight loss, bone pain and fatigue. The disease affects around one in a hundred thousand adults per year and, in the worst case, ends in acute leukemia with a short life expectancy.

The disease is triggered by mutations that cause the JAK2 tyrosine kinase to be permanently active, instead of only being activated when needed. This means that the bone marrow constantly receives signals to produce new blood cells. For about ten years now, inhibitors have been used that aim to limit the activity of JAK2.

The shortcomings of JAK2 inhibitor monotherapy

“The expectations we had for the treatment with JAK2 inhibitors have not been fully met,” says Professor Sara Christina Meyer, leader of the Myeloid Malignancies research team at the Department of Biomedicine at the University of Basel and Attending Physician in Hematology at the University Hospital of Basel (USB). While the symptoms improve, the proportion of leukemia cells in the blood remains high and after a few years the patients often no longer respond to the treatment. “We are addressing the question why this targeted therapy is not more effective.”

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