Acute Leukemias of Different Lineages Have Similar MLL Gene Fusions Encoding Related Chimeric Proteins Resulting from Chromosomal Translocation

The MLL gene, on human chromosome 11q23, undergoes chromosomal translocation in acute leukemias, resulting in gene fusion with AF4 (chromosome 4) and ENL (chromosome 19). We report here translocation of MLL with nine different chromosomes and two paracentric chromosome 11 deletions in early B cell,...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 1993-09, Vol.90 (18), p.8538-8542
Hauptverfasser: Corral, J., Forster, A., Thompson, S., Lampert, F., Kaneko, Y., Slater, R., Kroes, W. G., van der Schoot, C. E., W.-D. Ludwig, Karpas, A., Pocock, C., Cotter, F., Rabbitts, T. H.
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Sprache:eng
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Zusammenfassung:The MLL gene, on human chromosome 11q23, undergoes chromosomal translocation in acute leukemias, resulting in gene fusion with AF4 (chromosome 4) and ENL (chromosome 19). We report here translocation of MLL with nine different chromosomes and two paracentric chromosome 11 deletions in early B cell, B- or T-cell lineage, or nonlymphocytic acute leukemias. The mRNA translocation junction from 22 t(4;11) patients, including six adult leukemias, and nine t(11;19) tumors reveals a remarkable conservation of breakpoints within MLL, AF4, or ENL genes, irrespective of tumor phenotype. Typically, the breakpoints are upstream of the zinc-finger region of MLL, and deletion of this region can accompany translocation, supporting the der(11) chromosome as the important component in leukemogenesis. Partial sequence of a fusion between MLL and the AFX1 gene from chromosome X shows the latter to be rich in Ser/Pro codons, like the ENL mRNA. These data suggest that the heterogeneous 11q23 abnormalities might cause attachment of Ser/Pro-rich segments to the NH2terminus of MLL, lacking the zinc-finger region, and that translocations occur in early hematopoietic cells, before commitment to distinct lineages.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.90.18.8538