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The molecular biology of acute promyelocytic leukemia

  • James L. Slack
  • Robert E. Gallagher
Part of the Cancer Treatment and Research book series (CTAR, volume 99)

Abstract

In this chapter, our goal is to review and summarize current knowledge of the molecular biology of acute promyelocytic leukemia (APL). The cure of up to 75% of patients with APL [1,2] represents a remarkable and fascinating success story in medicine, and the treatment of APL with retinoic acid serves as a paradigm for the use of differentiation therapy in other types of human cancers. The high cure rate of APL is due in part to the extreme sensitivity of leukemic promyelocytes to the differentiating effects of the vitamin A derivative all -trans retinoic acid (ATRA), and it thus becomes critical to delineate the mechanisms by which APL cells respond to this and other retinoids. As discussed in detail below, the defining molecular aberration in APL is disruption of the alpha receptor for retinoic acid, RARα, and its reciprocal in-frame fusion with one of four partner genes (Table 1). As will become clear in this chapter, these fusion proteins, while they lack classic transforming activity, nevertheless have the capacity to disrupt hematopoiesis and effectively inactivate the molecular switch that governs promyelocytic maturation. Our focus here will thus be on the structure and function of the four fusion genes involved in APL pathogenesis, and on the mechanisms by which APL cells are sensitive to, and in some cases become resistant to, retinoids. It is hoped that a full understanding of the structure and function of these fusion molecules will provide a conceptual framework for a fuller understanding of the molecular signals that control both normal and malignant myelopoiesis.

Keywords

Retinoic Acid Acute Promyelocytic Leukemia Acute Promyelocytic Leukemia Cell Retinoic Acid Response Element Retinoic Acid Receptor Alpha 
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

© Kluwer Academic Publishers, Boston 1999

Authors and Affiliations

  • James L. Slack
  • Robert E. Gallagher

There are no affiliations available

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