title: Long-term support of hematopoiesis by a single stem cell clone in patients with paroxysmal nocturnal hemoglobinuria.
abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder characterized by clonal blood cells that are deficient in glycosylphosphatidylinositol-anchored proteins because of somatic mutations of the PIG-A gene. Many patients with PNH have more than one PNH clone, but it is unclear whether a single PNH clone remains dominant or minor clones eventually become dominant. Furthermore, it is unknown how many hematopoietic stem cells (HSCs) sustain hematopoiesis and how long a single HSC can support hematopoiesis in humans. To understand dynamics of HSCs, we reanalyzed the PIG-A gene mutations in 9 patients 6 to 10 years after the previous analyses. The proportion of affected peripheral blood polymorphonuclear cells (PMNs) in each patient was highly variable; it increased in 2 (from 50% and 65% to 98% and 97%, respectively), was stable in 4 (changed less than 20%), and diminished in 3 (94%, 99%, and 98% to 33%, 57%, and 43%, respectively) patients. The complexity of these results reflects the high variability of the clinical course of PNH. In all patients, the previously predominant clone was still present and dominant. Therefore, one stem cell clone can sustain hematopoiesis for 6 to 10 years in patients with PNH. Two patients whose affected PMNs decreased because of a decline of the predominant PNH clone and who have been followed up for 24 and 31 years now have an aplastic condition, suggesting that aplasia is a terminal feature of PNH.
authors.affiliation: Department of Immunoregulation/Research Institute for Microbial Diseases and the Research Foundation for Microbial Diseases, Osaka University, Japan. junnishi@acpub.duke.edu
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Nishimura Ji
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hirota
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kanakura
authors.forename: Takashi
authors.initials: T
authors.lastname: Machii
authors.forename: Takashi
authors.initials: T
authors.lastname: Kageyama
authors.forename: Shoichi
authors.initials: S
authors.lastname: Doi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.forename: Toru
authors.initials: T
authors.lastname: Masaoka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kanayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujii
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Inoue
authors.forename: Maki
authors.initials: M
authors.lastname: Kuwayama
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Inoue
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Ohishi
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D000328:Adult; D000368:Aged; D002999:Clone Cells / Q000737:chemistry / Q000473:pathology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006457:Hemoglobinuria, Paroxysmal / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009504:Neutrophils / Q000737:chemistry / Q000473:pathology
chemical_list: D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein