Identification of CBL, a proto-oncogene at 11q23.3, as a novel MLL fusion partner in a patient with de novo acute myeloid leukemia

Genes Chromosomes Cancer. 2003 Jun;37(2):214-9. doi: 10.1002/gcc.10204.


We have shown that the CBL gene at 11q23.3, telomeric to MLL, was fused to MLL in an adult patient with de novo acute myeloid leukemia (FAB-M1). Southern blot analysis indicated that the MLL rearrangement was involved in the chromosomal abnormality. cDNA panhandle polymerase chain reaction identified the fusion transcript, in which MLL exon 6 was fused in-frame with CBL exon 8. Long-distance PCR amplified the genomic junction region, which involved the fusion of the 3' portion of an Alu element in intron 6 of MLL with the 5' portion of an Alu element in intron 7 of CBL. The absence of extensive sequence similarity at both breakpoints of MLL and CBL indicated that the recombination was not generated through homologous recombination. MLL and CBL are located between STS markers D11S939 and D11S924. Analysis of the sequence demonstrated that the transcriptional orientation of both genes at 11q23.3 is from centromere to telomere. The results of Southern blotting in conjunction with fluorescence in situ hybridization suggest that the MLL-CBL fusion was the result of an interstitial deletion. CBL, a proto-oncogene, functions as a negative regulator of several receptor protein-tyrosine-kinase signaling pathways and as an adaptor protein in tyrosine phosphorylation-dependent signaling. CBL is the second gene at 11q23.3 found to fuse with MLL.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence / genetics
  • Base Sequence / genetics
  • Chromosome Breakage / genetics
  • Chromosomes, Human, Pair 11 / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics*
  • Molecular Sequence Data
  • Myeloid-Lymphoid Leukemia Protein
  • Oncogene Proteins, Fusion / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-cbl
  • Proto-Oncogenes*
  • Transcription Factors*
  • Ubiquitin-Protein Ligases*


  • DNA-Binding Proteins
  • KMT2A protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase
  • Proto-Oncogene Proteins c-cbl
  • Ubiquitin-Protein Ligases
  • CBL protein, human

Associated data

  • GENBANK/AY125965
  • GENBANK/AY126609