Reconstitution of NK cells expressing KIR3DL1 is associated with reduced NK cell activity and relapse of CML after allogeneic hematopoietic stem cell transplantation

Int J Hematol. 2020 May;111(5):733-738. doi: 10.1007/s12185-019-02809-5. Epub 2019 Dec 23.

Abstract

Although the prognosis of chronic myeloid leukemia (CML) in blastic crisis remains poor, some patients achieve long-term remission after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This may be attributable to graft-versus-leukemia (GVL) effects by donor lymphocytes, but their regulating mechanisms are unclear. Antitumor natural killer (NK) cell immunity is assumed to be important in CML, and we have previously shown that allelic polymorphisms of killer immunoglobulin-like receptors (KIRs) and histocompatibility leukocyte antigens (HLAs) are associated with the response of CML to tyrosine kinase inhibitors. Here, we report a case of CML in blastic phase who received HLA-matched but KIR3DL1 allelic-mismatched allo-HSCT. After transplant, decreased BCR-ABL transcript levels and enhanced NK cell activity were transiently observed. However, reconstitution of KIR3DL1-expressing NK cells occurred, which was associated with diminished NK cell activity and increased BCR-ABL. This case indicates the potential significance of KIR3DL1 in NK cell-mediated GVL activity following allo-HSCT. To the best of our knowledge, this is the first report to analyze the association between sequential KIR3DL1 expression and activity of NK cells after allo-HSCT. Selecting donors with KIR3DL1-null alleles may maintain competent GVL effects and provide improved outcomes in allo-HSCT for CML.

Keywords: Allogeneic peripheral blood stem cell transplantation; Chronic myeloid leukemia (CML); KIR3DL1; Killer immunoglobulin-like receptor; Natural killer cell (NK cell).

Publication types

  • Case Reports

MeSH terms

  • Allografts
  • Gene Expression*
  • Genes, abl / genetics
  • Graft vs Leukemia Effect / genetics
  • Graft vs Leukemia Effect / immunology
  • HLA Antigens
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Killer Cells, Natural / immunology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Neoplasm Recurrence, Local
  • Receptors, KIR3DL1 / genetics*
  • Transcription, Genetic
  • Treatment Outcome

Substances

  • HLA Antigens
  • KIR3DL1 protein, human
  • Receptors, KIR3DL1