Discovery of proangiogenic CD44+mesenchymal cancer stem cells in an acute myeloid leukemia patient's bone marrow

J Hematol Oncol. 2020 Jun 3;13(1):63. doi: 10.1186/s13045-020-00899-x.

Abstract

Here, we report a unique acute myeloid leukemia (AML) bone marrow-derived mesenchymal stem cell (MSC) with both mesenchymal and endothelial potential, which we have named Mesenchymal Cancer Stem Cells (MCSCs). These MCSCs are CD90-CD13-CD44+ and differ from MSCs in isolation, expansion, differentiation, immunophenotype, and cytokine release profile. Furthermore, blocking CD44 inhibited the proliferation and cluster formation of early MCSCs with lower ICAM-1 protein levels. Similar CD90-CD44+ cancer stem cells have been reported in both gastric and breast cancers, which grew in floating spheres in vitro and exhibited mesenchymal features and high metastatic/tumorigenic capabilities in vivo. Our novel discovery provides the first evidence that certain AMLs may be comprised of both hematopoietic and stromal malignant cells. Targeting MCSCs and their cytokine release has potential as a novel therapeutic approach in AML.

Keywords: Acute myeloid leukemia; Angiogenesis; CD44; Mesenchymal cancer stem cells; Mesenchymal stem cells; Microenvironment.

Publication types

  • Case Reports
  • Comparative Study
  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenic Proteins / metabolism
  • Antigens, Neoplasm / analysis*
  • Bone Marrow / pathology*
  • Cell Adhesion
  • Cell Separation
  • Cytokines / metabolism
  • Female
  • Humans
  • Hyaluronan Receptors / analysis*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Leukemia, Myelomonocytic, Acute / metabolism
  • Leukemia, Myelomonocytic, Acute / pathology*
  • Mesenchymal Stem Cells / chemistry
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology*
  • Neoplasm Proteins / metabolism
  • Neoplastic Stem Cells / chemistry
  • Neoplastic Stem Cells / classification
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Tumor Cells, Cultured

Substances

  • Angiogenic Proteins
  • Antigens, Neoplasm
  • CD44 protein, human
  • Cytokines
  • Hyaluronan Receptors
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins