Bone marrow infiltrated natural killer cells predicted the anti-leukemia activity of MCL1 or BCL2 inhibitors in acute myeloid leukemia

Mol Cancer. 2021 Jan 5;20(1):8. doi: 10.1186/s12943-020-01302-6.

Abstract

Acute myeloid leukemia (AML) is still incurable due to its heterogeneity and complexity of tumor microenvironment. It is imperative therefore to understand the molecular pathogenesis of AML and identify leukemia-associated biomarkers to formulate effective treatment strategies. Here, we systematically analyzed the clinical characters and natural killer (NK) cells portion in seventy newly-diagnosis (ND) AML patients. We found that the proportion of NK cells in the bone marrow of ND-AML patients could predict the prognosis of patients by analyzing the types and expression abundance of NK related ligands in tumor cells. Furthermore, MCL1 inhibitor but not BCL2 inhibitor combined with NK cell-based immunotherapy could effectively improve the therapeutic efficiency via inhibiting proliferation and inducing apoptosis of AML primary cells as well as cell lines in vitro. There results provide valuable insights that could help for exploring new therapeutic strategies for leukemia treatment.

Keywords: AML; BCL2 inhibitor; Immunotherapy; MCL1 inhibitor; NK cells.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bone Marrow / pathology*
  • Female
  • Humans
  • Killer Cells, Natural / immunology*
  • Leukemia, Myeloid, Acute / immunology*
  • Male
  • Middle Aged
  • Myeloid Cell Leukemia Sequence 1 Protein / antagonists & inhibitors*
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Receptors, KIR / metabolism*
  • Survival Analysis
  • Young Adult

Substances

  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, KIR