PrincipaI Investigator: Kasiani Myers, MD
Key Personnel: Lee Grimes, PhD, Carolyn Lutzko, PhD
There is an incomplete understanding of the events leading to the development of bone marrow failure and leukemia. This limits our ability to accurately diagnose and develop treatments. Inherited bone marrow failure syndromes are a diverse group of rare genetic disorders in which children are at very high risk for bone marrow failure and other types of cancer, especially acute myeloid leukemia. These children often exhibit signs of bone marrow failure before age ten or even as early as at birth, and some develop cancer before age twenty.
Current treatments are quite limited, focusing mainly on supportive care and screening for known risks, or quite toxic, such as bone marrow transplant with its many potential complications and mortality. Risk of cancer and marrow failure, however, is not the same in all of these disorders, and therefore treatment approaches may be very different depending on the exact genetic cause. Despite the discovery of genes leading to many of these disorders, there remain a large portion of children for whom the genetic cause remains unknown. A better understanding of the genetic basis of these diseases is crucial to guide clinical care and develop better treatment strategies. In this project we will sequence all of the protein-coding genes in patients with inherited bone marrow failure of unknown cause and compare them to these same genes in their healthy family members to discover genetic differences that may be disease causing. These candidate genes will be rigorously screened in mouse and human cells in the laboratory to verify their potential as causative genetic changes for these disorders. This exciting science will discover new genetic causes for bone marrow failure syndromes, create novel diagnostic tools for clinicians, and open innovative avenues for research into the mechanisms of bone marrow failure and leukemia development. This will lead to earlier diagnosis, improve clinical care now, and facilitate the development of novel potentially less toxic therapies to prevent and treat bone marrow failure and leukemia in children as well as adults.