Emerging Role for MicroRNAs in Acute Promyelocytic Leukemia

  • C. Nervi
  • F. Fazi
  • A. Rosa
  • A. Fatica
  • I. Bozzoni
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 313)


Hematopoiesis is highly controlled by lineage-specific transcription factors that, by interacting with specific DNA sequences, directly activate or repress specific gene expression. These transcription factors have been found mutated or altered by chromosomal translocations associated with leukemias, indicating their role in the pathogenesis of these malignancies. The post-genomic era, however, has shown that transcription factors are not the only key regulators of gene expression. Epigenetic mechanisms such as DNA methylation, posttranslational modifications of histones, remodeling of nucleosomes, and expression of small regulatory RNAs all contribute to the regulation of gene expression and determination of cell and tissue specificity. Deregulation of these epigenetic mechanisms cooperates with genetic alterations to the establishment and progression of tumors. MicroRNAs (miRNAs) are negative regulators of the expression of genes involved in development, differentiation, proliferation, and apoptosis. Their expression appears to be tissue-specific and highly regulated according to the cell’s developmental lineage and stage. Interestingly, miRNAs expressed in hematopoietic cells have been found mutated or altered by chromosomal translocations associated with leukemias. The expression levels of a specific miR-223 correlate with the differentiation fate of myeloid precursors. The activation of both pathways of transcriptional regulation by the myeloid lineage-specific transcription factor C/EBPα (CCAAT/enhancer-binding protein-α), and posttranscriptional regulation by miR-223 appears essential for granulocytic differentiation and clinical response of acute promyelocytic leukemia (APL) blasts to all-trans retinoic acid (ATRA). Together, this evidence underlies transcription factors, chromatin remodeling, and miRNAs as ultimate determinants for the correct organization of cell type-specific gene arrays and hematopoietic differentiation, therefore providing new targets for the diagnosis and treatment of leukemias.


Acute Myeloid Leukemia Retinoic Acid Treatment Myeloid Cell Line Hematopoietic Differentiation Granulocytic Differentiation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • C. Nervi
    • 1
  • F. Fazi
    • 1
  • A. Rosa
    • 2
  • A. Fatica
    • 2
  • I. Bozzoni
    • 2
  1. 1.Department of Histology and Medical EmbryologyUniversity of Rome “La Sapienza” and San Raffaele Bio-medical Park FoundationRomeItaly
  2. 2.Institute Pasteur Cenci-Bolognetti, Department of Genetics and Molecular Biology and I.B.P.M.University of Rome “La Sapienza”RomeItaly

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