New research recently showed that there is a potential to enhance therapeutic effects on chronic leukemia by additionally preventing a specific signaling pathway.
A Technology Networks report said in this chronic disease, hindering the overactive kinase JAK2 by a targeting treatment approach only mitigates the symptoms, although it cannot truly change the disease's course.
The study's findings published in Leukemia are quite convincing that they are already being integrated into clinical research in what the researchers described as the "bench-to-bedside" method.
Essentially, chronic leukemia forms myeloproliferative neoplasms. This means that the body constantly generates too many blood cells like erythrocytes, granulocytes, and platelets.
JAK2 Tyrosine Kinase
This may result in thrombosis, enlarged spleen, and constitutional symptoms like weight loss, fatigue, and pain.
More so, a similar MyScience report said, the illness impacts around one in every hundred thousand adults each year, in the worst case, ends having acute leukemia with a short life expectancy.
The chronic illness is triggered by mutations causing the JAK2 tyrosine kinase to be active permanently, rather than just being activated when needed.
According to the Myeloid Malignancies research team leader, Professor Sara Christina Meyer, from the Department of Biomedicine and the University of Basel, their expectations for treating JAK2 inhibitors have not been fully met.
Meyer, also the Attending Physician in Hematology at the University Hospital of Basel added, while symptoms improve, the leukemia cells' proportion in the blood stays high, and after several years, the patient frequently doesn't respond to the treatment anymore. She explained, they are addressing the issue of why such a targeted treatment is not more efficient.
MAPK Signaling Pathway
Meyer's group concentrates on the MAPK signaling pathway, which is involved in several cancers' development and is regulated by JAK2 in myeloproliferative neoplasms.
As a result, elaborated Professor Meyer, they have discovered in previous research that this signaling pathway stays active despite JAK2 inhibition and continues stimulating hematopoiesis.
To identify the leading cause of the problem, the study authors, as a result, deactivated ERK1/2, an essential component of the MAPK signaling pathway, on top of the JAK2, and examined if such combined targeting is more effective in treating leukemia.
3 Deactivating Approaches for Leukemia Treatment
To do the deactivation, the researchers used three different systems. First, they established leukemia cell cultures, then used mouse models for myeloid leukemia, and third, they used blood and bone marrow specimens from patients.
For the deactivation of ERK1/2, the study authors used inhibitors that have recently become available and, in particular, blocked ERK1/2.
One of the compounds, and an approved JAK2 inhibitor, were provided by Novartis for the research. In the mouse models, the researchers deactivated the genes as well, for ERK1/2
through the use of molecular biology approaches.
In all three test methods, the JAK2 inhibitor treatment's efficacy was enhanced when combined with the targeting of ERK1/2. This was observed by the decline in the production of blood cells in the mouse model and the decrease in spleen size.
Specifically, Meyer finds it specifically encouraging that combined treatment lessens the proportion of leukemia cells in both the bone marrow and the blood, which is rarely the case with JAK2 inhibitors, as generally described in the National Library of Medicine, as single agents, and could modify the course of the disease in the longer term.
Because of these promising outcomes, the innovative combination treatment approach has promptly been applied into an international phase 1/2 clinical trial and is already being utilized in a small number of patients. Meyer is expecting the first results in the next couple of months.
Related information about leukemia treatment is shown on Khanacademymedicine's YouTube video below:
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