title: Recent advances in understanding clonal haematopoiesis in aplastic anaemia.
abstract: Acquired aplastic anaemia (AA) is an immune-mediated bone marrow failure disorder inextricably linked to clonal haematopoiesis. The majority of AA patients have somatic mutations and/or structural chromosomal abnormalities detected as early as at diagnosis. In contrast to other conditions linked to clonal haematopoiesis, the clonal signature of AA reflects its immune pathophysiology. The most common alterations are clonal expansions of cells lacking glycophosphotidylinositol-anchored proteins, loss of human leucocyte antigen alleles, and mutations in BCOR/BCORL1, ASXL1 and DNMT3A. Here, we present the current knowledge of clonal haematopoiesis in AA as it relates to aging, inherited bone marrow failure, and the grey-zone overlap of AA and myelodysplastic syndrome (MDS). We conclude by discussing the significance of clonal haematopoiesis both for improved diagnosis of AA, as well as for a more precise, personalized approach to prognostication of outcomes and therapy choices.
authors.affiliation: Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Stanley
authors.affiliation: Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Blood and Marrow Transplant Program, Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Olson
authors.affiliation: Comprehensive Bone Marrow Failure Center, Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Division of Hematology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Daria V
authors.initials: DV
authors.lastname: Babushok
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D001855:Bone Marrow Diseases / Q000235:genetics; D000080983:Bone Marrow Failure Disorders; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells / Q000502:physiology; D003937:Diagnosis, Differential; D005260:Female; D005819:Genetic Markers; D006410:Hematopoiesis / Q000235:genetics*; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics; D006801:Humans; D057131:Immune Evasion / Q000235:genetics; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics; D011379:Prognosis; D012008:Recurrence; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins
keywords: 
  CHIP
  ; 
  MDS
  ; aplastic anaemia; bone marrow failure; clonal haematopoiesis