A closer look at specific therapeutic strategies in leukemia

Leukemia & Lymphoma
Manuel Martínez-MancillaPatricio Gariglio

Abstract

Leukemia-associated fusion genes are detected in a significant proportion of newly diagnosed cases, where genes encoding transcription factors are usually found at one of the breakpoints. Activated fusion proteins, such as PML-RARalpha and AML1-ETO, have been shown to inhibit cellular differentiation by recruitment of nuclear corepressor complexes, which maintain local histone deacetylase (HDAC) in a variety of hematologic lineage-specific gene promoters. This HDAC-dependent transcriptional repression appears as a common pathway in the development of leukemia and could represent an important target for new therapeutic agents. On the other hand, the Bcr-Abl oncoprotein shows high tyrosine kinase activity and deregulates signal transduction pathways involved normally in both apoptosis and proliferation. This aberrant activity is affected by signal transduction inhibitors (STIs), which block or prevent the oncogenic pathway. In this review, we present a closer look at our understanding of both the reversible transcriptional repression controlled by HDAC and the deregulated Bcr-Abl signal transduction. In addition, the application of low molecular weight drugs for human leukemia treatment based in this knowledge results in durable ...Continue Reading

References

Oct 1, 1994·Molecular and Cellular Biology·Z M MuK S Chang
Oct 9, 1997·The New England Journal of Medicine·M S TallmanP H Wiernik
Nov 20, 1998·Molecular and Cellular Biology·B LutterbachS W Hiebert
Jan 29, 1999·Journal of the National Cancer Institute·P le CoutreC Gambacorti-Passerini
Apr 29, 1999·The New England Journal of Medicine·C L Sawyers
Jul 31, 1999·Annals of Internal Medicine·S FaderlH M Kantarjian
Oct 12, 2000·Nature Cell Biology·A GuoP P Pandolfi
Apr 5, 2001·The New England Journal of Medicine·B J DrukerC L Sawyers
Sep 25, 2001·Blood·J M Goldman, B J Druker
Jan 12, 2002·Nature Medicine·Laura J Van 't Veer, Daphne De Jong
Feb 8, 2002·Cell·Paolo Salomoni, Pier Paolo Pandolfi
Apr 19, 2002·Biochimica Et Biophysica Acta·Jerald P Radich
May 29, 2002·Oncogene·Wilson H Miller, Samuel Waxman
Feb 8, 2003·Current Opinion in Genetics & Development·Soyoung Lee, Clemens A Schmitt
Mar 8, 2003·Blood·Leonidas C Platanias
Apr 2, 2003·Nature Medicine·Terence H Rabbitts, Martin R Stocks
Oct 29, 2003·Seminars in Hematology·Torsten HaferlachClaudia Schoch

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