title: Erythroid dysplasia, megaloblastic anemia, and impaired lymphopoiesis arising from mitochondrial dysfunction.
abstract: Recent reports describe hematopoietic abnormalities in mice with targeted instability of the mitochondrial genome. However, these abnormalities have not been fully described. We demonstrate that mutant animals develop an age-dependent, macrocytic anemia with abnormal erythroid maturation and megaloblastic changes, as well as profound defects in lymphopoiesis. Mice die of severe fatal anemia at 15 months of age. Bone-marrow transplantation studies demonstrate that these abnormalities are intrinsic to the hematopoietic compartment and dependent upon the age of donor hematopoietic stem cells. These abnormalities are phenotypically similar to those found in patients with refractory anemia, suggesting that, in some cases, the myelodysplastic syndromes are caused by abnormalities of mitochondrial function.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Chen
authors.forename: T Daniel
authors.initials: TD
authors.lastname: Logan
authors.forename: Maryann L
authors.initials: ML
authors.lastname: Hochberg
authors.forename: Suresh G
authors.initials: SG
authors.lastname: Shelat
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Wilding
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Kujoth
authors.forename: Tomas A
authors.initials: TA
authors.lastname: Prolla
authors.forename: Mary A
authors.initials: MA
authors.lastname: Selak
authors.forename: Mondira
authors.initials: M
authors.lastname: Kundu
authors.forename: Martin
authors.initials: M
authors.lastname: Carroll
authors.forename: James E
authors.initials: JE
authors.lastname: Thompson
mesh_terms: D000367:Age Factors; D000749:Anemia, Megaloblastic / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D016026:Bone Marrow Transplantation; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D004195:Disease Models, Animal; D041905:Erythroid Cells / Q000473:pathology; D004920:Erythropoiesis / Q000235:genetics; D054629:Genome, Mitochondrial; D006801:Humans; D038041:Lymphopoiesis / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D028361:Mitochondrial Diseases / Q000150:complications* / Q000235:genetics / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D017354:Point Mutation
chemical_list: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C498803:Polg protein, mouse