Graft-vs-host disease is a common and potentially deadly complication following bone marrow transplants, in which immune cells from the donated bone marrow attack the recipientâ€™s body.
Winship Cancer Instituteâ€™s Ned Waller and researchers from Childrenâ€™s Healthcare of Atlanta and Yerkes National Primate Research Center were part of a recent Science Translational Medicine paper that draws a bright red circle around aurora kinase A as a likely drug target in graft-vs-host disease.
Aurora kinases are enzymes that control mitosis, the process of cell division, and were first discovered in the 1990s in yeast, flies and frogs. Now drugs that inhibit aurora kinase A are in clinical trials for several types of cancer, and clinicans are planning to examine whether the same type of drugs could help with graft-vs-host disease.
Leslie Kean, a pediatric cancer specialist at Seattle Childrenâ€™s who was at Emory until 2013, is the senior author of the STM paper. Seattle Childrens’ press releaseÂ says that Kean wears a bracelet around her badge from a pediatric patient cured of leukemia one year ago, but who is still in the hospital due to complications from graft-vs-host. Read more
As a followup to yesterday’s post on following troublemaker cells in patients with lupus, we’d like to highlight a recent paper in Blood that takesÂ a similar approach to studying how the immune system comes back after bone marrow/blood stem cell transplant.
Leslie Kean, MD, PhD
The paper’sÂ findings have implications for making this type ofÂ transplant safer and preventing graft-versus-host disease.Â In a bone marrow/blood stem cell transplant, to fight cancer, doctors are essentially clearing out someone’s immune system and then “planting” a newÂ oneÂ with the help of a donor. What this paper shows is how much CMV (cytomegalovirus) distorts the new immune system.
CMV is often thought of asÂ harmless — most adults in the United States have been infected with CMV by age 40 and don’t get sick because of it. But in this situation, CMV’s emergence from the shadows forces some of the new TÂ cells to multiply, dominating the immune system so much that it creates gaps in the rest of the T cell repertoire, which canÂ compromise protective immunity. Other seemingly innocuous viruses like BK cause trouble in immunosuppressed patients afterÂ kidney transplant.
The senior author, Leslie Kean, moved from Emory to Seattle Children’s Hospital in 2013, and her team began these studies here in 2010Â (a host of Emory/Winship hematologists and immunologists are co-authors).Â This paperÂ is sort of a mirror image of the Nature Immunology paper on lupus because it also uses next-generation sequencing to follow immune cells with DNA rearrangements — in this case, T cells. Read more