Prognostic and therapeutic role of CLEC12A in acute myeloid leukemia

Blood Rev. 2019 Mar:34:26-33. doi: 10.1016/j.blre.2018.10.003. Epub 2018 Nov 1.

Abstract

CLEC12A has recently been identified as an antigen, expressed on leukemic stem cells and leukemic blasts. Given the fact that this expression profile seems stable throughout diagnosis, treatment and relapse on leukemic blasts and leukemic stem cells, CLEC12A can be considered a highly potent and reliable marker for the detection of measurable residual disease and therefore applicable for risk stratification and prognostication in AML. Low CLEC12A expression on leukemic blasts seems to be independently associated with lower likelihood of achieving complete remission after 1 cycle of induction chemotherapy, shorter event free survival, as well as overall survival, indicating potential prognostic properties of CLEC12A expression itself. Lack of expression on the normal hematopoietic stem and progenitor cells, in contrast to CD123 and CD33, might result in less toxicity regarding cytopenias, making CLEC12A an interesting target for innovating immunotherapies, including monoclonal and bispecific antibodies, antibody-drug conjugates and CAR-T cells therapy.

Keywords: Acute myeloid leukemia; Antibody; Antibody-drug conjugate; BiTE; Bispecific antibody; CLEC12A; CLL-1; Chimeric antigen receptor; Immunotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use
  • Biomarkers, Tumor*
  • Disease Management
  • Gene Expression Regulation, Leukemic
  • Humans
  • Immunotherapy
  • Lectins, C-Type / antagonists & inhibitors
  • Lectins, C-Type / chemistry
  • Lectins, C-Type / genetics*
  • Lectins, C-Type / metabolism
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy*
  • Molecular Targeted Therapy
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / metabolism
  • Prognosis
  • Receptors, Mitogen / antagonists & inhibitors
  • Receptors, Mitogen / chemistry
  • Receptors, Mitogen / genetics*
  • Receptors, Mitogen / metabolism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • CLEC12A protein, human
  • Lectins, C-Type
  • Receptors, Mitogen