Apoptotic stimuli initiate MLL-AF9 translocations that are transcribed in cells capable of division

Christopher J. Betti, Michael J. Villalobos, Manuel O. Diaz, Andrew T M Vaughan

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Activation of apoptosis introduces a site-specific break within intron 11 of the MLL gene. Using the CD95 apoptotic signaling pathway in human lymphoblastoid cells, the 5′ fragment of MLL undergoes translocation to intron 4 of AF9 and the proleukemogenic MLL-AF9 fusion gene created is transcribed. Both the breaks in MLL and transcription of the MLL-AF9 fusion gene are suppressed in the presence of the broad spectrum caspase inhibitor, zVAD.fmk. Duplicate cells containing sequence identical MLL-AF9 fusion junctions were identified within a cell population that had recovered from apoptosis. This indicated that cells harboring a translocation initiated by apoptotic cleavage had divided. These data are consistent with a novel pathogenic role for the apoptotic program where translocations with leukemogenic potential are created within cells that have the capacity to divide.

Original languageEnglish (US)
Pages (from-to)1377-1381
Number of pages5
JournalCancer Research
Volume63
Issue number6
StatePublished - Mar 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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