Identifying Inherited and Acquired Genetic Factors Involved in Poor Stem Cell Mobilization and Donor-Derived Malignancy

Biol Blood Marrow Transplant. 2016 Nov;22(11):2100-2103. doi: 10.1016/j.bbmt.2016.08.002. Epub 2016 Aug 4.

Abstract

Analysis of the clinical characteristics of hematopoietic stem cell transplant (HSCT) donors has proven beneficial for identifying cases of heritable hematopoietic disorders. This study examines poor peripheral blood hematopoietic stem cell mobilization after granulocyte colony-stimulating factor administration among 328 donors as a potential marker for suspected familial predisposition to myeloid malignancies. Here, we present data comparing the clinical characteristics of poor-mobilizing versus nonpoor-mobilizing donors and the results of panel-based sequencing of hematopoietic genes in poor-mobilizing donors. From this analysis, we identified a novel case of a donor-derived myelodysplastic syndrome in an HSCT recipient that is consistent with clonal evolution of TET2-mutated clonal hematopoiesis of indeterminate potential (CHIP) within the donor. This study demonstrates the potential risk of using hematopoietic stem cells from a donor with CHIP and raises the question of whether there should be increased screening measures to identify such donors.

Keywords: Clonal hematopoiesis of indeterminate potential; Donor-derived leukemia; TET2 mutation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Donors*
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics
  • Female
  • Genetic Predisposition to Disease
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Hematopoiesis / genetics
  • Hematopoietic Stem Cell Mobilization / standards*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / genetics
  • Neoplasms / etiology
  • Neoplasms / genetics*
  • Pedigree
  • Proto-Oncogene Proteins / genetics
  • Young Adult

Substances

  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Granulocyte Colony-Stimulating Factor
  • TET2 protein, human