pre-myeloid cancer and bone marrow failure clinic study

Conditions: Myeloid Malignancy; Inherited Bone Marrow Failure Syndrome; Clonal Expansion; Cytopenia; Bone Marrow Failure Syndrome; Clonal Cytopenia of Undetermined Significance; Clonal Hematopoiesis of Indeterminate Potential; Hematologic Neoplasms; Hematopoietic and Lymphatic System Neoplasm; Hereditary Neoplastic Syndrome; Idiopathic Cytopenia of Undetermined Significance; Idiopathic Dysplasia of Uncertain Significance; Low Risk Myelodysplastic Syndrome

Summary: this clinical trial tests next generation sequencing (ngs) for the detection of precursor features of pre-myeloid cancers and bone marrow failure syndromes. ngs is a procedure that looks at relevant cancer associated genes and what they do. finding genetic markers for pre-malignant conditions may help identify patients who are at risk of pre-myeloid cancers and bone marrow failure syndromes and lead to earlier intervention.

primary objectives: i. to use genomics and functional translational studies to diagnose, prognosticate and potentially offer therapeutic directives for patients with precursor features of myeloid neoplasms (myelodysplastic syndrome \[mds\], myeloproliferative neoplasms \[mpn\], mds/mpn overlap syndrome) and germline predisposition/bone marrow failure states, who do not meet the criteria for the diagnosis of these cancers as of yet. ii. to identify patients with precursor myeloid malignancies and bone marrow failure syndromes. iii. to examine the utility of ngs methods for discovery of targets or pathways involved in precursor features of myeloid cancer and bone marrow failure. iv. to use clinomics/genomics to better understand pathobiology and risk of disease progression. v. to help better understand the implications of variants of unknown significance using computational biology and functional studies. vi. to utilize normal, age and sex matched controls to validate genetic and epigenetic testing carried out under this protocol (essential for accurate data analysis). vii. to assess frailty in patients with clonal hematopoiesis in order to validate genetic and epigenetic testing completed under this protocol as objective assessments of frailty and aging in comparison to standard of care frailty and geriatric assessments. outline: participants may undergo blood sample collection, a bone marrow biopsy, a skin punch biopsy, hair follicle collection, a buccal swab, and/or saliva collection for ngs analysis on study. patients may additionally undergo clinical assessment and may receive genetic counseling on study.

Eligibility criteria:
inclusion criteria: * patients with idiopathic cytopenias of unclear significance (icus) * patients with clonal hematopoiesis of indeterminate significance (clonal hematopoiesis of indeterminate potential \[chip\]), including the recently described chip syndrome called vexas (vacuoles, e1 ubiquitin ligase, x chromosomal, autoimmune and somatic) * patients with clonal cytopenias of undetermined significance (ccus) * marrow failure syndromes with myeloid malignancy predisposition - telomere dysfunction, chromosomal breakage disorders * germ line inherited syndromes with risk for malignant transformation - gata2, cebpa, etv-6, runx1, jak2, pf6, etc. * low risk mds (idiopathic dysplasia of unclear significance) * family member of a patient with one of the above conditions * patient at high risk or suspected of developing one of the above conditions exclusion criteria: * patients under 18 years of age