A systematic description of MLL fusion gene formation

Rebecca L. Wright, Andrew T M Vaughan

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Rearrangements of the MLL gene involve multiple partners and are implicated in both therapy related acute leukemia [tAL] and infant acute leukemia. For these diseases, recently compiled clinical data confirms an elevated frequency of such breakpoints within a 4. kb tract between exon 11 and a region of structural instability adjacent to exon 12. Linked primarily to cases of tAL, interference with topoisomerase II activity may either contribute to the initial DNA lesion directly or indirectly by, for example, providing a physical block to transcription progression. Alternatively, sites of fragmentation may be mis-repaired, guided by intergenic spliced transcripts of the participating genes. Co-transcription of MLL and potential fusion partners may provide the localization that enhances the probability of gene interaction. An indirect role for the leukemogenic activity of topoisomerase II inhibitors would imply that the negative consequences of their use may be separated from their therapeutic effects.

Original languageEnglish (US)
Pages (from-to)283-291
Number of pages9
JournalCritical Reviews in Oncology/Hematology
Volume91
Issue number3
DOIs
StatePublished - 2014

Keywords

  • Acute leukemia
  • AICDA
  • MLL
  • Recombinome
  • Topoisomerase II
  • Transcription factory
  • Translocation

ASJC Scopus subject areas

  • Oncology
  • Hematology
  • Geriatrics and Gerontology
  • Medicine(all)

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