title: Increased expression of anti-apoptosis genes in peripheral blood cells from patients with paroxysmal nocturnal hemoglobinuria.
abstract: Resistance to apoptosis has been described in neutrophils from patients with PNH and related hematologic disorders (aplastic anemia, myelodysplastic syndrome), but its molecular basis is not understood. Using gene expression analysis, PNH granulocytes had relative overexpression of four anti-apoptosis genes (human A1, hHR23B, Mcl-1, and RhoA) compared to normal controls. These findings were confirmed by RT-PCR analysis and observed in both peripheral blood granulocytes and mononuclear cells of patients with PNH. Anti-apoptosis gene upregulation may confer resistance to apoptosis in PNH and related disorders, and provide a common compensatory mechanism after bone marrow injury that allows survival and growth of remaining hematopoietic stem cells.
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. matthew.heeney@tch.harvard.edu
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Heeney
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ormsbee
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.forename: Thad A
authors.initials: TA
authors.lastname: Howard
authors.forename: Carlos M
authors.initials: CM
authors.lastname: DeCastro
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
mesh_terms: D017209:Apoptosis; D001853:Bone Marrow / Q000378:metabolism; D002470:Cell Survival; D015870:Gene Expression; D006098:Granulocytes / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D012313:RNA