Instructive role of MLL-fusion proteins revealed by a model of t(4;11) pro-B acute lymphoblastic leukemia

Research output: Contribution to journalArticlepeer-review


  • Shan Lin
  • Roger T. Luo
  • Jon Kerry
  • Mark Wunderlich
  • Toshihiko Lmamura
  • Joseph J. Kaberlein
  • Ahmad Rayes
  • Mark J. Althoff
  • John Anastasi
  • Maureen M. O’Brien
  • Amom Ruhikanta Meetei
  • Thomas A. Milne
  • James Mulloy
  • Michael J. Thirman

Colleges, School and Institutes


The t(4;11)(q21;q23) fuses MLL to AF4, the most common MLL-fusion partner. Here we show hat MLL fused to murine Af4, highly conserved with human AF4, produces high-titer retrovirus permitting efficient transduction of human CD34+ cells and generating a faithful model of t(4;11) proB ALL that fully recapitulates the immunophenotypic and molecular aspects of the disease. MLL-Af4 induces a B-ALL distinct from MLL-AF9 through differential genomic target binding of the fusion proteins leading to specific gene expression patterns. MLL-Af4 cells can assume a myeloid state under environmental pressure but retain lymphoid-lineage potential. Such incongruity was also observed in t(4;11) patients who evaded CD19-directed therapy by undergoing myeloid-lineage switch. Our model provides a valuable tool to unravel the pathogenesis of MLL-AF4 leukemogenesis.   


Original languageEnglish
Pages (from-to)737–749
Number of pages13
JournalCancer Cell
Issue number5
Publication statusPublished - 14 Nov 2016


  • MLL-AF4, acute lymphoblastic leukemi, chimeric fusion proteins, mouse models of cancer, acquired resistance to targeted therapy, species specificity of oncogenes