A brief, but comprehensive, guide to clonal evolution in aplastic anemia

Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):457-466. doi: 10.1182/asheducation-2018.1.457.


Acquired aplastic anemia (AA) is an immune-mediated bone marrow aplasia that is strongly associated with clonal hematopoiesis upon marrow recovery. More than 70% of AA patients develop somatic mutations in their hematopoietic cells. In contrast to other conditions linked to clonal hematopoiesis, such as myelodysplastic syndrome (MDS) or clonal hematopoiesis of indeterminate potential in the elderly, the top alterations in AA are closely related to its immune pathogenesis. Nearly 40% of AA patients carry somatic mutations in the PIGA gene manifested as clonal populations of cells with the paroxysmal nocturnal hemoglobinuria phenotype, and 17% of AA patients have loss of HLA class I alleles. It is estimated that between 20% and 35% of AA patients have somatic mutations associated with hematologic malignancies, most characteristically in the ASXL1, BCOR, and BCORL1 genes. Risk factors for evolution to MDS in AA include the duration of disease, acquisition of high-risk somatic mutations, and age at AA onset. Emerging data suggest that several HLA class I alleles not only predispose to the development of AA but may also predispose to clonal evolution in AA patients. Long-term prospective studies are needed to determine the true prognostic implications of clonal hematopoiesis in AA. This article provides a brief, but comprehensive, review of our current understanding of clonal evolution in AA and concludes with 3 cases that illustrate a practical approach for integrating results of next-generation molecular studies into the clinical care of AA patients in 2018.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia, Aplastic* / blood
  • Anemia, Aplastic* / etiology
  • Anemia, Aplastic* / genetics
  • Anemia, Aplastic* / physiopathology
  • Genes, MHC Class I
  • Hematopoiesis / genetics
  • Humans
  • Membrane Proteins / blood
  • Membrane Proteins / genetics
  • Mutation*
  • Myelodysplastic Syndromes / blood
  • Myelodysplastic Syndromes / complications
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / physiopathology
  • Proto-Oncogene Proteins / blood
  • Proto-Oncogene Proteins / genetics
  • Repressor Proteins / blood
  • Repressor Proteins / genetics
  • Risk Factors


  • ASXL1 protein, human
  • BCOR protein, human
  • BCORL1 protein, human
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • phosphatidylinositol glycan-class A protein