Linking miRNA regulation to BCR-ABL expression: the next dimension

Cancer Cell. 2008 Jun;13(6):467-9. doi: 10.1016/j.ccr.2008.05.013.

Abstract

The introduction of tyrosine kinase inhibitors in the treatment of BCR-ABL1-rearranged malignancies has revolutionized therapy, but the prognosis for acute leukemias remains suboptimal. In this issue of Cancer Cell, Bueno et al. (2008) add a new dimension to the regulation of ABL1 expression. The authors demonstrate that ABL1 is a direct target of miR-203, miR-203 is silenced by genetic and epigenetic mechanisms in hematopoietic malignancies expressing either ABL1 or BCR-ABL1, and restoration of miR-203 expression reduces ABL1 and BCR-ABL1 levels and inhibits cell proliferation. These findings may have broad implications for mechanisms underlying malignant transformation in hematopoietic and other malignancies.

Publication types

  • Comment

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Methylation*
  • Fusion Proteins, bcr-abl / metabolism*
  • Gene Expression Regulation, Leukemic
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Lymphoma, T-Cell / genetics
  • Lymphoma, T-Cell / metabolism
  • Lymphoma, T-Cell / pathology
  • Lymphoproliferative Disorders / drug therapy
  • Lymphoproliferative Disorders / enzymology
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / metabolism*
  • Lymphoproliferative Disorders / pathology
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • MicroRNAs
  • Protein Kinase Inhibitors
  • abl-bcr fusion protein, human
  • Fusion Proteins, bcr-abl
  • Proto-Oncogene Proteins c-abl