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Molecular Genetics of APL

  • Lourdes Mendez
  • Ming Chen
  • Pier Paolo Pandolfi
Chapter

Abstract

The balanced translocation t(15;17)(q22;q12) is the genetic hallmark of acute promyelocytic leukemia (APL) juxtaposing the N-terminus of the promyelocytic leukemia gene (PML) with the C-terminus of retinoic acid receptor alpha (RARα) to produce the PML-RARα fusion oncoprotein. APL has the unique distinction of being the first and only malignancy in which high cure rates are achieved with targeted therapy, through the combination of two naturally derived compounds, all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). The efficacy of these two agents against the disease and their synergistic and curative potential was predicted by transgenic murine models, which were equally instrumental in unlocking the molecular pathogenesis of APL.

Keywords

Acute promyelocytic leukemia PML RARα RXR Retinoic acid signaling PML nuclear bodies PML-RARα PLZF-RARα Transgenic mouse models 

Notes

Acknowledgments

We would like to thank current members of the Pandolfi laboratory for critical discussion and Lauren Southwood and Elizabeth Stack for editing and administrative support. This work is supported in part by funding from the National Cancer Institute (R01CA142874 and R35-CA197529 to P.P.P.).

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Lourdes Mendez
    • 1
  • Ming Chen
    • 1
  • Pier Paolo Pandolfi
    • 1
  1. 1.Department of Medicine and PathologyCancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA

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