Bone marrow failure as a risk factor for clonal evolution: prospects for leukemia prevention.
Patients with bone marrow failure syndromes are at risk for the development of clonal neoplasms, including paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia (MDS), and acute myelogenous leukemia (AML). Approximately 10% to 20% of those who survive acquired aplastic anemia will develop a clonal disease within the decade following their diagnosis. The relative risk of clonal neoplasms is very significantly increased in children and adults with inherited bone marrow failure syndromes as well. Until recently, the mechanisms underlying clonal evolution have been opaque, but a sufficient amount of evidence has now accumulated to support a model in which cells resistant to extracellular apoptotic cues are selected from the stem cell pool. Indeed, in the past two years this paradigm has been validated in preclinical models that are robust enough to reconsider new therapeutic objectives in aplastic states and to support the planning and development of rationally designed leukemia prevention trials.
Bagby
Grover C
GC
OHSU Cancer Institute, Oregon Health & Sciences University, 3181 SW Sam Jackson Park Road, CR-145, Portland, OR 97239, USA. grover@ohsu.edu
Meyers
Gabrielle
G
D001855:Bone Marrow Diseases / Q000473:pathology*; D006801:Humans; D007938:Leukemia / Q000517:prevention & control*; D012307:Risk Factors