Bone morphogenetic proteins regulate differentiation of human promyelocytic leukemia cells

Leuk Res. 2013 Jun;37(6):705-12. doi: 10.1016/j.leukres.2013.03.002. Epub 2013 Mar 23.

Abstract

We investigated the role of bone morphogenetic proteins (BMPs) in suppression of all-trans retinoic acid (ATRA)-mediated differentiation of leukemic promyelocytes. In NB4 and HL60 cell lines, BMPs reduced the percentage of differentiated cells, and suppressed PU.1 and C/EBPε gene expression induced by ATRA. BMP and ATRA synergized in the induction of ID genes, causing suppression of differentiation. In primary acute promyelocytic leukemia bone-marrow samples, positive correlation of PML/RARα and negative of RARα with the expression of BMP-4, BMP-6 and ID genes were found. We concluded that BMPs may have oncogenic properties and mediate ATRA resistance by a mechanism that involves ID genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 2 / pharmacology
  • Bone Morphogenetic Protein 2 / physiology
  • Bone Morphogenetic Protein 4 / pharmacology
  • Bone Morphogenetic Protein 4 / physiology
  • Bone Morphogenetic Protein 6 / pharmacology
  • Bone Morphogenetic Protein 6 / physiology
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / pharmacology
  • Bone Morphogenetic Proteins / physiology*
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Gene Expression Regulation, Leukemic / drug effects
  • Gene Expression Regulation, Leukemic / genetics
  • Granulocyte Precursor Cells / drug effects*
  • Granulocyte Precursor Cells / metabolism
  • Granulocyte Precursor Cells / physiology
  • HL-60 Cells
  • Humans
  • Leukemia, Promyelocytic, Acute / genetics
  • Leukemia, Promyelocytic, Acute / pathology
  • Leukemia, Promyelocytic, Acute / physiopathology*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / physiology
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Tretinoin / pharmacology
  • Tumor Cells, Cultured

Substances

  • BMP2 protein, human
  • BMP4 protein, human
  • BMP6 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein 6
  • Bone Morphogenetic Proteins
  • Oncogene Proteins, Fusion
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • Tretinoin