In utero rearrangements in the trithorax-related oncogene in infant leukaemias

Nature. 1993 May 27;363(6427):358-60. doi: 10.1038/363358a0.


The majority (approximately 75%) of infant acute leukaemias have a reciprocal translocation between chromosome 11q23 and one of several partner chromosomes. The gene at 11q23 (named MLL, ALL-1, HRX or HTRX-1; refs 2-6) has been cloned and shares homology with the Drosophila developmental gene trithorax. Rearrangements of this gene (called HRX here) occur in introns and cluster in a region of approximately 10 kb; individual patients have different breakpoints. Here we describe three pairs of infant twins with concordant leukaemia who each share unique (clonal) but non-constitutive HRX rearrangements in their leukaemic cells, providing evidence that the leukaemogenic event originates in utero and unequivocal support for the intra-placental 'metastasis' hypothesis for leukaemia concordance in twins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, Pair 11
  • Clone Cells
  • DNA-Binding Proteins / genetics*
  • Diseases in Twins / genetics*
  • Dosage Compensation, Genetic
  • Female
  • Gene Rearrangement*
  • Gene Rearrangement, B-Lymphocyte
  • Gene Rearrangement, T-Lymphocyte
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Infant
  • Male
  • Myeloid-Lymphoid Leukemia Protein
  • Neoplasm Metastasis
  • Oncogenes*
  • Placenta
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / embryology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Pregnancy
  • Proto-Oncogenes*
  • Transcription Factors*
  • Twins, Monozygotic


  • DNA-Binding Proteins
  • KMT2A protein, human
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase