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

• DOI: 10.1038/363358a0
• Publication Date: 2003-08-12T00:27:12Z
• Authors: Anthony M. Ford; Susan A. Ridge; Maria E. Cabrera; Hazem Mahmoud; C. Michael Steel; Li C. Chan; Mel Greaves
• Keywords: Male; Placenta; Twins; Diseases In Twins - Genetics; Gene Rearrangement, T-Lymphocyte; Chromosomes; Monozygotic; 03 medical and health sciences; 0302 clinical medicine; Genetic; Pregnancy; Dosage Compensation, Genetic; Proto-Oncogenes; Diseases in Twins; Humans; Pair 11; Neoplasm Metastasis; Gene Rearrangement, B-Lymphocyte; Gene Rearrangement; Chromosomes, Human, Pair 11; B-Lymphocyte; Infant; Precursor Cell Lymphoblastic Leukemia-Lymphoma - Embryology - Genetics; Twins, Monozygotic; Histone-Lysine N-Methyltransferase; Oncogenes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Clone Cells; DNA-Binding Proteins; T-Lymphocyte; Dosage Compensation; Female; Dna-Binding Proteins - Genetics; Myeloid-Lymphoid Leukemia Protein; Human; Transcription Factors

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.