In utero rearrangements in the trithorax-related oncogene in infant leukaemias.
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.
Leukaemia Research Fund Centre, Chester Beatty Laboratories, London, UK.
A M
AM
Ford
S A
SA
Ridge
M E
ME
Cabrera
H
H
Mahmoud
C M
CM
Steel
L C
LC
Chan
M
M
Greaves
D002880:Chromosomes, Human, Pair 11; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics*; D004200:Diseases in Twins / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D015321:Gene Rearrangement; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein; D009362:Neoplasm Metastasis; D009857:Oncogenes; D010920:Placenta; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000196:embryology* / Q000235:genetics*; D011247:Pregnancy; D011519:Proto-Oncogenes; D014157:Transcription Factors; D014430:Twins, Monozygotic
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase