Bone marrow transplantation restores immune system function and prevents lymphoma in Atm-deficient mice.
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.
Bagley
Jessamyn
J
Transplantation Biology Research Center, Massachusetts General Hospital, MGH-East, 149-5210 13th St, Boston, MA 02129, USA.
Cortes
Maria L
ML
Breakefield
Xandra O
XO
Iacomini
John
J
D000818:Animals; D001260:Ataxia Telangiectasia / Q000276:immunology* / Q000628:therapy*; D064007:Ataxia Telangiectasia Mutated Proteins; D016026:Bone Marrow Transplantation; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007156:Immunologic Memory; D016399:Lymphoma, T-Cell / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D013953:Thymus Neoplasms / Q000517:prevention & control*; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases