Functional analysis of the two reciprocal fusion genes MLL-NEBL and NEBL-MLL reveal their oncogenic potential

Cancer Lett. 2013 May 10;332(1):30-4. doi: 10.1016/j.canlet.2012.12.023. Epub 2013 Jan 20.


MLL gene aberrations are frequently diagnosed in infant acute myeloid leukemia (AML). We previously described the MLL-NEBL and NEBL-MLL genomic fusions in an infant AML patient with a chromosomal translocation t(10;11)(p12;q23). NEBL was the second Nebulin family member (LASP1, NEBL) which was found to be involved in MLL rearrangements. Here, we report on our attempts to unravel the oncogenic properties of both fusion genes. First, RT-PCR analyses revealed the presence of the MLL-NEBL and NEBL-MLL mRNAs in the diagnostic sample of the patient. Next, expression cassettes for MLL-NEBL and NEBL-MLL were cloned into a sleeping beauty vector backbone. After stable transfection, the biological effects of MLL-NEBL, NEBL-MLL or the combination of both fusion proteins were investigated in a conditional cell culture model. NEBL-MLL but also co-transfected cells displayed significantly higher growth rates according to the data obtained by cell proliferation assay. The focus formation experiments revealed differences in the shape and number of colonies when comparing MLL-NEBL, NEBL-MLL- and co-transfected cells. The results obtained in this study suggest that the reciprocal fusion genes of the Nebulin gene family might be of biological importance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Proliferation
  • Cell Shape
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Gene Fusion*
  • Genotype
  • HEK293 Cells
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Infant
  • LIM Domain Proteins / genetics*
  • LIM Domain Proteins / metabolism
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Mice
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Myeloid-Lymphoid Leukemia Protein / metabolism
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Phenotype
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection


  • Carrier Proteins
  • Cytoskeletal Proteins
  • KMT2A protein, human
  • LIM Domain Proteins
  • NEBL protein, human
  • Oncogene Proteins, Fusion
  • RNA, Messenger
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase