One of our organization’s foundational goals was to help lobby for and orchestrate a comprehensive, longitudinal (patients will be followed over time), centralized, natural history study. A study where genomic and phenotypic data could have bio-informatics applied to the dataset to allow any qualified investigators access, globally. Thanks to the tireless efforts of one of our Scientific Advisors, Dr. Paul Liu, this will now become reality. We are absolutely thrilled to share with you a groundbreaking new Research Study that will be taking place at the National Institutes of Health commencing fall of 2018. In addition to providing a foundation for future research in the field, the Research Center will provide cutting-edge, best-in-kind therapeutics to those with RUNX1 FPD/AML who go on to develop leukemia, and at no cost to the patient.
Following is a brief review of the relevancy of this study to our disease understanding, along with a more detailed description of the Clinical Research Center and Study. In the coming months we will be reaching out to affected families, clinicians and researchers following FPD/AML families, genetic testing companies, AML groups, and more. If you are interested in participating in this study in any format, either personally or via recommendation, you will be taking an active role in pushing the field one step towards finding a cure. All data will be secured at a governmental level and kept completely anonymous for the purpose of research.
Dr. Paul Liu, NHGRI, Dr. Dennis Hickstein, NCI, Dr. Lea Cunningham (Clinical Director), ‘The National Institutes of Health RUNX1-FPD Clinical Research Center and Study’.
We know that a germline RUNX1 mutation causes a syndrome known as familial platelet disorder with associated myeloid malignancies (FPDMM, or simply FPD. Note that originally it was believed that only AML resulted from the platelet disorder, hence the original name FPD/AML; whereas, it is now understood that varied types of acute leukemias may result.) Patients with FPD have a life-long risk of developing hematological malignancies with variable clinical presentation and disease penetrance among families with different germline mutation types, and even between affected individuals within the same family. Currently, there are no good biomarkers or assays to predict the development of leukemia, and the fact that many FPD patients do not go on to develop leukemia suggests that the original RUNX1 mutation in itself is insufficient for leukemogenesis; additional mutations (both somatic and inherited), followed by clonal evolution are needed.
To better understand the natural history of FPD, and to identify individuals at higher risk of developing leukemia, we are establishing a new clinical research program at the National Institutes of Health (NIH) Clinical Center in Bethesda, Maryland dedicated to the study of FPD. This program has three components. The first component involves identifying or confirming RUNX1 mutations in index cases and family members by DNA sequencing. The second part consists of a longitudinal natural history study with phenotyping of FPD patients and identifying secondary mutations leading to progression of the disease. The third part consists of a therapeutic or treatment component with a uniform regimen for allogeneic hematopoietic stem cell transplantation. Collaborating and supporting components include the NIH Intramural Sequencing Center for genomic sequencing to identify secondary mutations, NIH CC Laboratory of Medicine for CLIA-certified diagnosis, genetic counseling service, and other clinical laboratories. There will be biospecimen and data sharing between this program and investigators in the extramural program. This program is designed to improve the understanding of FPD and enhance the care of these patients.
Dr. Liu is an expert on the development of leukemia using genetic and genomic approaches, and has been an instrumental advisor and friend of The RUNX1 Research Program. In his role as the Deputy Scientific Director of the NIH’s NHGRI (National Human Genome Research Institute), he advocated for the creation of the Clinical Research Center and Study within the NIH’s Intramural Research Program. He will oversee its overall organization. We are pleased to announce that Dr. Lea Cunningham, a pediatric hematologist and oncologist with fellowship training from Hopkins and NIH and experience as an independent physician-scientist at St. Jude Children's Research Hospital, will direct the overall clinical activities for this program. Dr. Dennis Hickman is a Senior Investigator at the National Cancer Institute’s Center for Cancer Research in the Experimental Transplantation and Immunology Branch, as well as being Head of the Molecular Oncology and Gene Transfer Section. Dr. Hickstein has headed the GATA2 Center and Study at NCI and will serve as Senior Advisor.
To ensure the field at large would benefit from the data using the latest in data analytics, we have enlisted the expertise of Dr. Casey Greene of the Perelman School of Medicine at the University of Pennsylvania’s Greene Lab (greenelab.com) and Childhood Cancer Data Lab (CCDL). Dr. Greene has been funded by Alex’s Lemonade Stand Foundation at the CCDL to democratize cancer genomics analysis. He is developing a system to capture and analyze complex datasets in a user-friendly interface for access to any qualified researcher globally.
Our organization’s role in the Research Center and Study will be to encourage families worldwide to participate in the program and to encourage clinicians to collaborate. Moreover, we will aim to fund subsequent research proposals that make use of data generated by the Research Center and Study.
If you are clinician with FPD families, or are interested in hearing more about the Center and Study and possibly participating, please ensure you are on our communications distribution list. We will update you when the Program is live.