Comprehensive genetic analysis of donor cell derived leukemia with KMT2A rearrangement

Pediatr Blood Cancer. 2018 Feb;65(2). doi: 10.1002/pbc.26823. Epub 2017 Sep 17.


Background: Donor cell leukemia (DCL) occurs after allogeneic hematopoietic stem cell transplantation. Several mechanisms, including occult leukemic/preleukemic subclones in the donor graft and germline predisposition to leukemia, are proposed to be associated with DCL's molecular pathogenesis. We report a comprehensive genetic analysis of a patient with KMT2A-rearranged DCL after allogeneic bone marrow transplantation for refractory cytopenia of childhood.

Procedure: We performed a whole-exome sequencing of the recipient's peripheral blood before transplant and the donor's peripheral blood and the recipient's bone marrow at the time of DCL diagnosis. RNA sequencing was also performed to detect fusion genes in DCL blasts.

Results: There were no germline mutations that were associated with a predisposition to leukemia in the recipient and donor. Furthermore, there were no detectable somatic alterations except KMT2A-MLLT10 and other related gene fusions in DCL. KMT2A-MLLT10 was not detectable in the donor's bone marrow.

Conclusion: We propose a novel pattern of the molecular pathogenesis of DCL solely involving a genetic mutation acquired after transplant with no identifiable genetic factor related to the donor and recipient.

Keywords: acute myeloid leukemia; donor cell leukemia; stem cell transplantation.

Publication types

  • Case Reports

MeSH terms

  • Allografts
  • Blast Crisis / genetics*
  • Bone Marrow Transplantation*
  • Child, Preschool
  • Female
  • Gene Rearrangement*
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Infant
  • Leukemia / genetics*
  • Male
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Pancytopenia / genetics
  • Pancytopenia / therapy*
  • Tissue Donors*
  • Transcription Factors / genetics


  • KMT2A protein, human
  • MLLT10 protein, human
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase