Longitudinal Studies of Patient With FPDMM

FPDMM, Inherited Hematological Diseases, Rare Diseases

inherited hematological diseases, Rare Diseases, Hematological Malignancies, Cancer, Acute Myeloid Leukemia, Natural History

Background: Genes tell the body and its cells how to work. Familial platelet disease (FPD) or FPD with associated malignancies (FPDMM) is caused by a variant in the gene RUNX1. People with this disease may have problems with their blood and bleed for a long time when they are injured. Researchers want to learn more about RUNX1 variants and FPD. Objective: To learn more about FPD in people with RUNX1 variants to lead to better diagnosis, monitoring, and treatment. Eligibility: People any age with a suspected or confirmed RUNX1 variant People who have a family member with the variant Design: All participants will be screened with a phone call and a blood, saliva, or cheek cell sample. Participants with a suspected or confirmed variant will have 1 visit. It will last about 2 days. They will then have visits at least once a year. Visits will include: * Medical history and physical exam * Blood tests or saliva sample * Possible skin biopsy: A small piece of the participant s skin will be removed. * Bone marrow aspiration or biopsy: The participant s bone marrow will be removed by needle from a large bone such as the hip bone. * Possible apheresis: Blood will be removed from the body and certain blood cells will be taken out. The rest of the blood is returned to the body. Between visits, participants with a suspected or confirmed variant will keep a diary of disease symptoms and signs. Samples from all participants may be used for genetic testing

Study Description: This is a natural history study of patients with familial platelet disorder with associated myeloid malignancies (FPDMM), also known as FPD and FPDAML, who undergo diagnostic clinical tests, diagnostic genetic tests, and yearly follow-up visits; and the collected biological samples will be used for biomedical research to understand the disease mechanism, including genomic sequencing. Unaffected family members will participate and serve as controls for studies of the affected family members. Objectives: Primary Objective: To identify and follow patients with germline variants in the RUNX1 gene, which leads to FPDMM, an autosomal dominant disorder, with the hope of identifying biomarkers that can predict which patients will progress and develop malignancies, as well as the timing of the progression and the severity of the malignancies. Secondary Objectives: To identify secondary gene mutations that may impact clinical presentation, disease severity, and progression to malignancies. Secondary gene discovery will distinguish subpopulations of patients and may inform clinical care and improve diagnosis. To profile non-hematopoietic presentations of FPDMM. To identify genetic basis for patients with FPDMM-like clinical presentation but without known RUNX1 variants. To longitudinally assess psychosocial experiences, psychosocial functioning, and health related quality of life of persons living with RUNX1-FPD. Exploratory Objective: Identify new therapeutic strategies. Endpoints: Primary Endpoint: The primary endpoint is progression to malignancy in patients with FPD (FPDMM). Patients who develop malignancies will continue in the study for longitudinal observation.

None listed

United States