Bone marrow transplantation restores immune system function and prevents lymphoma in Atm-deficient mice

Abstract Ataxia-telangiectasia (A-T) is a human autosomal recessive disease caused by mutations in the gene encoding ataxia-telangiectasia mutated (ATM). A-T is characterized by progressive cerebellar degeneration, variable immunodeficiency, and a high incidence of leukemia and lymphoma. Recurrent sino-pulmonary infections secondary to immunodeficiency and hematopoietic malignancies are major causes of morbidity and mortality in A-T patients. In mice, an introduced mutation in Atm leads to a phenotype that recapitulates many of the symptoms of A-T, including immune system abnormalities and susceptibility to malignancy. Here we show that the replacement of the bone marrow compartment in Atm knockout mice (Atm-/-) using a clinically relevant, nonmyeloablative host-conditioning regimen can be used to overcome the immune deficiencies and prevent the malignancies observed in these mice. Therefore, bone marrow transplantation may prove to be of therapeutic benefit in A-T patients. (Blood. 2004;104:572-578)