Biology Lessons from Human Disease — The Pathophysiology of Bone Marrow Failure

Clinical observations of patients with bone marrow failure have led to insights into the biology of autoimmunity, viral pathogenesis, and cancer. Historically, aplastic anemia has been regarded in isolation and as heterogeneous and refractory to laboratory investigation. Bone marrow destruction is now understood to be effected by the immune system, and patients respond to immunosuppressive therapies, which have markedly prolonged survival. The etiology is poorly understood, but epidemiology has suggested environmental risk factors rather than drugs and exposure to toxins. B19 parvovirus, while not etiologic of aplastic anemia, is directly toxic to erythroid progenitors, and both acute and persistent infection result in profound anemia. Marrow failure syndromes can evolve into myelodysplasia and leukemia. Telomere shortening, whether genetic, iatrogenic, or physiologic, appears to be the common link between organ failure and malignant transformation.