Kinase binding activity analysis using DiscoverX Kinomescan profiling. 1.1-1.4: Off-target kinase activity was assessed using a commercially available screen from Eurofins. All four test compounds were tested at high concentrations (1 uM) to maximize the sensitivity of the screen. DiscoverX Kinomescan utilizes an active site-specific competition assay to measure the binding activity of test compounds against 450 human kinases. This assay does not utilize ATP and is therefore not a functional kinase activity screen. 1.5-1.6: Allogeneic groups of animals were administered various test compounds at the indicated dose regimens, and spleen and thymus tissue samples were collected 4 hours after the final dose to determine BTK and ITK by drug target binding. Determined occupancy level. Occupancy was determined in the spleen for BTK and in the thymus for ITK using an ELISA format with MSD detection and selective irreversible probes for each target (see Methods for details). reference). Error bars are shown as SEM. P Value 0.01 to 0.05 = *, P Value 0.001 to 0.01 = **, P Value 0.0001 to 0.001 = ***, P Value <0.0001 = ****, NS is not significant. credit: Bone marrow transplantation (2023). DOI: 10.1038/s41409-023-02001-8
Researchers at the University of Missouri School of Medicine have discovered a potential treatment for two common complications after bone marrow transplants.
Bone marrow transplantation is a treatment that can potentially cure leukemia and other blood cancers by transferring a type of stem cell from a donor to a patient. However, a common complication of bone marrow transplants is something called graft-versus-host disease (GvHD), in which the donated cells treat the recipient’s cells as an unknown threat or attack.
Acute GvHD occurs immediately after transplantation and often affects the skin, intestines, and liver. Chronic GVHD can occur at any time after transplantation and usually affects the skin, mouth, lungs, intestines, muscles, or joints.
In a recent study appear in Transplantation and cell therapyThe MU research team administered a drug called defibrotide, which is commonly used to treat blocked blood vessels in the liver, to mice undergoing bone marrow transplants. The researchers found that the drug protected cells lining blood vessels that are typically damaged in patients with acute GvHD.
“Treatment with defibrotide reduced acute GvHD and significantly improved survival,” said Dr. Senthilnathan Palaniyandhi, assistant professor of medicine at the University of Missouri School of Medicine. “Through its anti-inflammatory and endothelial protective effects, this treatment reduced the severity of acute GvHD without compromising the transplanted immune cells that fight leukemia.”
In another study was announced on Bone marrow transplantation, the research team targeted chronic GvHD. They found that introducing different types of BTK/ITK kinase inhibitors reduced the severity of chronic GvHD and improved mouse survival.
“We have found that a combination of kinase inhibitors is effective in treating skin diseases caused by chronic GVHD,” said Dr. Kremlin, chief of the Division of Hematology and Medical Oncology at the University of Missouri School of Medicine and director of the Ellis Fischel Cancer Center at MU Healthcare. said Gerhard Hildebrandt, MD. “Mice treated with a combination of kinase inhibitors showed a significant reduction in chronic complications associated with bone marrow transplantation.”
These findings demonstrate that drugs that protect the cells lining blood vessels are effective in reducing acute GvHD, and that kinase inhibition holds promise as a treatment for chronic GvHD.
“A better understanding of how to manage GvHD is essential for clinically effective bone marrow transplantation at Ellis Fischel Cancer Center and around the world,” Hildebrandt said. “Our laboratory is one of a small number of laboratories dedicated to solving the mysteries of GVHD to make bone marrow transplantation more effective, advancing research, saving lives, and making improvements.” This demonstrates the University of Missouri Health System’s commitment to
For more information:
Senthilnathan Palaniyandi et al, Role of defibrotide in the prevention of graft-versus-host disease in a mouse model after allogeneic hematopoietic cell transplantation, Transplantation and cell therapy (2023). DOI: 10.1016/j.jtct.2023.07.023
Senthilnathan Palaniyandi et al, Combined inhibition of Tec kinases BTK and ITK is beneficial in ameliorating chronic graft-versus-host disease in murine scleroderma. Bone marrow transplantation (2023). DOI: 10.1038/s41409-023-02001-8
Quote: Researchers discover potential treatment for common complications after bone marrow transplant (February 14, 2024) https://medicalxpress.com/news/2024-02-potential-treatments-common- Retrieved February 24, 2024 from complication-bone.html
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