title: Myelodysplastic syndrome macrophages have aberrant iron storage and heme oxygenase-1 expression.
abstract: Iron overload and transfusion dependance portend poor risk in myelodysplastic syndromes (MDS); bone marrow macrophages store iron and limit oxidative damage through heme oxygenase-1 (HO1). We assessed iron stores and macrophage HO1 expression in MDS using image analysis of intact diagnostic bone marrow biopsies and qualitative scoring of marrow aspirate iron among 129 cytopenic patients, 67 with MDS and 62 similarly aged patients with benign cytopenias. Using double immunofluorescence and sequential iron and immunohistochemistry staining, we showed that marrow iron colocalizes with HO1 and H-ferritin to CD163 + macrophages. Marrow iron was elevated in MDS independent of transfusion status, a finding of potential utility in distinguishing benign cytopenia from MDS. Among MDS patients only, CD163 + macrophage density and HO1 and H-ferritin expression by CD163 + macrophages increased in tandem with marrow iron. High HO1 was significantly associated with shorter overall survival among MDS patients independent of IPSSR and history of transfusion.
authors.affiliation: a Department of Pathology , Stanford University School of Medicine , Stanford , CA , USA ;|b Kaiser Permanente, Department of Pathology , Santa Clara Homestead , Santa Clara , CA , USA.
authors.forename: Grant
authors.initials: G
authors.lastname: Nybakken
authors.affiliation: a Department of Pathology , Stanford University School of Medicine , Stanford , CA , USA ;
authors.forename: Dita
authors.initials: D
authors.lastname: Gratzinger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D001803:Blood Transfusion; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005293:Ferritins / Q000378:metabolism*; D005500:Follow-Up Studies; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000150:complications; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D060787:Neoplasm Grading; D010088:Oxidoreductases; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D005293:Ferritins; D007501:Iron; C454461:FTH1 protein, human; D010088:Oxidoreductases; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: Heme oxygenase; iron; macrophage; myelodysplastic syndromes