Acute leukemias of different lineages have similar MLL gene fusions encoding related chimeric proteins resulting from chromosomal translocation

Journal Article · Wed Sep 15 00:00:00 EDT 1993 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.90.18.8538· OSTI ID:5105020

Corral, J; Forster, A; Thompson, S; Rabbitts, T H ^[1]; Lampert, F ^[2]; Kaneko, Y ^[3]; Slater, R; Kroes, W G ^[4]; Van Der Schoot, C E ^[5]; Ludwig, W D ^[6]; Karpas, A ^[7]; Pocock, C; Cotter, F ^[8]

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1. Medical Research Council Laboratory of Molecular Biology, Cambridge (United Kingdom)
2. Kinderklinik-Universitaet Giessen (Germany)
3. Saitama Cancer Centre, Saitama (Japan)
4. Univ. of Amsterdam (Netherlands)
5. Central Laboratory of the Netherlands Red Cross, Amsterdam (Netherlands)
6. Institut fur Humangenetik und Antrhopologie, Heidelberg (Germany)
7. Univ. of Cambridge (United Kingdom)
8. Institute of Child Health, London (United Kingdom)

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). The authors 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 22t(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 NH[sub 2] terminus of MLL, lacking the zinc-finger region, and that translocation occurs in early hematopoietic cells, before commitment to distinct lineages. 36 refs., 2 figs.

• OSTI ID: 5105020
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 90:18; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GENES
TRANSLOCATION
HUMAN CHROMOSOMES
LEUKEMIA
GENE MUTATIONS
PROTEINS
CHROMOSOME BREAKAGE
HUMAN CHROMOSOME 19
HUMAN X CHROMOSOME
CHROMOSOMAL ABERRATIONS
CHROMOSOMES
DISEASES
HETEROCHROMOSOMES
IMMUNE SYSTEM DISEASES
MUTATIONS
NEOPLASMS
ORGANIC COMPOUNDS
X CHROMOSOME
550400* - Genetics