VWD patient-derived endothelial cells isolated from human peripheral blood are plated into a micro-chamber to detect defects in the storage, release, and function of VWF after stimulation with phorbol 12-myristate 13-acetate. Cells pictured are stained for VWF( yellow), nuclei( teal), and CD31( blue).
LEUKEMIA world, including laboratories in Utah, Michigan, Canada, and Italy, we would not have been able to find these mutations.”
“ Their work demonstrates how a multidisciplinary approach can strengthen our knowledge and expand the field,” says Lia Gore, MD, Chief of Pediatric Oncology.“ It also helps explain a previously unidentified genetic disorder that has allowed us to better watch patients who might be at risk.”
Dr. Di Paola and his colleagues published their findings in Nature Genetics in 2015. Other studies with similar findings were published at the same time. A more recent study showed that ETV6 germline mutations are common in up to 1 percent of individuals with ALL.
Today, Dr. Di Paola and collaborators at Emory University, and in Colorado and Utah, are working to understand the molecular mechanisms of this disease through a newly generated mouse model to further study the gene mutation and its effects on blood.
Why is von Willebrand disease worse for some and not others?
Dr. Di Paola has been asking himself this question for the last 20 years. He studies von Willebrand disease( VWD), the most common bleeding disorder among adults and children, characterized by highly variable symptoms, even within members of the same family.
Scientists have long understood the genetic basis of VWD. But, according to Dr. Di Paola, they still don’ t understand why, among those who have moderate to mild disease, some bleed more severely than others.
Dr. Di Paola and his team are conducting one of the largest studies in the world to understand the complexities of the genetics and biology of the disease. Their study included an Amish family with 2,000 members, from which he collected 900 samples over the last decade.
Using modern genomic techniques, his team made a multi-gene array where,“ It appears there might be a combination of gene variants that might make you more susceptible to bleeding,” Dr. Di Paola says.
Identifying those genes could help target treatment for patients with VWD, adjusting as necessary to prevent bleeding complications.
“ When it comes to most common forms of VWD, we were all still in the dark ages,” says Dr. Di Paola.“ With this genetic array we made, we hope we are starting to understand the genetic underpinnings that make this disease so variable.”
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