Mechanisms of leukemia translocations

Jac A. Nickoloff, Leyma P. De Haro, Justin Wray, Robert Hromas

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations

Abstract

Purpose of Review: This review highlights recent findings about the known DNA repair machinery, its impact on chromosomal translocation mechanisms and their relevance to leukemia in the clinic. Recent Findings: Chromosomal translocations regulate the behavior of leukemia. They not only predict outcome but they define therapy. There is a great deal of knowledge on the products of leukemic translocations, yet little is known about the mechanism by which those translocations occur. Given the large number of DNA double-strand breaks that occur during normal progression through the cell cycle, especially from V(D)J recombination, stalled replication forks or failed decatenation, it is surprising that leukemogenic translocations do not occur more frequently. Fortunately, hematopoietic cells have sophisticated repair mechanisms to suppress such translocations. When these defenses fail leukemia becomes far more common, as seen in inherited deficiencies of DNA repair. Analyzing translocation sequences in cellular and animal models, and in human leukemias, has yielded new insights into the mechanisms of leukemogenic translocations. Summary: New data from animal models suggest a two hit origin of leukemic translocations, where there must be both a defect in DNA double-strand break repair and a subsequent failure of cell cycle arrest for leukemogenesis.

Original languageEnglish (US)
Pages (from-to)338-345
Number of pages8
JournalCurrent Opinion in Hematology
Volume15
Issue number4
DOIs
StatePublished - Jul 2008
Externally publishedYes

Keywords

  • Chromosomal translocations
  • DNA double-strand break repair
  • Nonhomologous endjoining
  • V(D)J recombination

ASJC Scopus subject areas

  • Hematology

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