From the Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
An immune pathophysiology for acquired aplastic anemia (AA) has been inferred from the responsiveness of the patients to immunosuppressive therapies and experimental laboratory data. To address the transcriptome of hematopoietic cells in AA, we undertook GeneChip analysis of the extremely limited numbers of progenitor and stem cells in the marrow of patients with this disease. We pooled total RNA from highly enriched bone marrow CD34 cells of 36 patients with newly diagnosed AA and 12 healthy volunteers for analysis on oligonucleotide chips. A large number of genes implicated in apoptosis and cell death showed markedly increased expression in AA CD34 cells, and negative proliferation control genes also had increased activity. Conversely, cell cycle progress–enhancing genes showed low expression in AA. Cytokine/chemokine signal transducer genes, stress response genes, and defense/immune response genes were up-regulated, as anticipated from other evidence of the heightened immune activity in AA patients' marrow. In summary, detailed genetic analysis of small numbers of hematopoietic progenitor cells is feasible even in marrow failure states where such cells are present in very small numbers. The gene expression profile of primary human CD34 hematopoietic stem cells from AA was consistent with a stressed, dying, and immunologically activated target cell population. Many of the genes showing differential expression in AA deserve further detailed analysis, including comparison with other marrow failure states and autoimmune disease.
Prognostic significance of cyclin D1 expression in resected stage I, II non-small cell lung cancer in Arabs
Cardiac-Specific Overexpression of Diacylglycerol Kinase Prevents Gq Protein-Coupled Receptor Agonist-Induced Cardiac Hypertrophy in Transgenic Mice
CD8+ T Lymphocytes Regulate the Arteriogenic Response to Ischemia by Infiltrating the Site of Collateral Vessel Development and Recruiting CD4+ Mononuclear Cells Through the Expression of Interleukin-
Altered Expression of Disintegrin Metalloproteinases and Their Inhibitor in Human Dilated Cardiomyopathy
Clinical Expression of Plakophilin-2 Mutations in Familial Arrhythmogenic Right Ventricular Cardiomyopathy
Decreased Neurotrophin TrkB Receptor Expression Reduces Lesion Size in the Apolipoprotein E–Null Mutant Mouse
Nox1 Overexpression Potentiates Angiotensin II-Induced Hypertension and Vascular Smooth Muscle Hypertrophy in Transgenic Mice
Rapamycin, but Not FK-506, Increases Endothelial Tissue Factor Expression
Dimethylarginine Dimethylaminohydrolase Overexpression Suppresses Graft Coronary Artery Disease
Increased Expression of Mineralocorticoid Effector Mechanisms in Kidney Biopsies of Patients With Heavy Proteinuria