Delta-like Homologue 1 and Its Role in the Bone Marrow Niche and Hematologic Malignancies

Clin Lymphoma Myeloma Leuk. 2014 Dec;14(6):451-5. doi: 10.1016/j.clml.2014.06.019. Epub 2014 Jun 23.

Abstract

Delta-like homologue 1 (DLK1) is an imprinted gene, that acts as a Notch pathway antagonist. It is deregulated in solid and blood cancers, conferring malignant cells a cancer stem cell-like phenotype. DLK1 is important for normal hematopoiesis and for bone marrow homeostasis, because it directly affects the differentiation of mesenchymal stem cells into the nonhematopoietic components. It is possible that the resulting abnormal biology of mesenchymal stem cells promotes leukemic blasts survival providing also a sanctuary against chemotherapeutic agents. In this review, the effects of DLK1 on mesenchymal stem cells and the bone marrow microenvironment with perspectives are discussed.

Keywords: DLK1; Hematopoietic stem cells; Leukemia; Mesenchymal stem cells; Stroma.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Marrow / metabolism*
  • Bone Marrow / pathology
  • Calcium-Binding Proteins
  • Hematologic Neoplasms / genetics*
  • Hematologic Neoplasms / metabolism*
  • Hematopoiesis / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Stem Cell Niche / genetics*
  • Tumor Microenvironment / genetics

Substances

  • Calcium-Binding Proteins
  • DLK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins