Therapeutically targeting SELF-reinforcing leukemic niches in acute myeloid leukemia: A worthy endeavor?

Am J Hematol. 2016 May;91(5):507-17. doi: 10.1002/ajh.24312. Epub 2016 Apr 4.

Abstract

A tight relationship between the acute myeloid leukemia (AML) population and the bone marrow (BM) microenvironment has been convincingly established. The AML clone contains leukemic stem cells (LSCs) that compete with normal hematopoietic stem cells (HSCs) for niche occupancy and remodel the niche; whereas, the BM microenvironment might promote AML development and progression not only through hypoxia and homing/adhesion molecules, but also through genetic defects. Although it is still unknown whether the niche influences treatment results or contains any potential target for treatment, this dynamic AML-niche interaction might be a promising therapeutic objective to significantly improve the AML cure rate.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Benzylamines
  • Bone Marrow / pathology
  • Cell Hypoxia / drug effects
  • Cell Lineage
  • Chemokine CXCL12 / antagonists & inhibitors
  • Chemokine CXCL12 / immunology
  • Chemokine CXCL12 / physiology
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Cord Blood Stem Cell Transplantation
  • Cyclams
  • Diphosphonates / therapeutic use
  • Disease Models, Animal
  • Heterocyclic Compounds / therapeutic use
  • Humans
  • Intercellular Signaling Peptides and Proteins / physiology
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Mice
  • Molecular Targeted Therapy*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / physiology
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / immunology
  • Receptors, CXCR4 / physiology
  • Stem Cell Niche / drug effects*
  • Stromal Cells / classification
  • Stromal Cells / drug effects
  • Stromal Cells / pathology
  • Transplantation, Heterologous
  • Tumor Microenvironment / drug effects

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Benzylamines
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Cyclams
  • Diphosphonates
  • Heterocyclic Compounds
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Receptors, CXCR4
  • plerixafor