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Metallothionein gene cluster is split by chromosome 16 rearrangements in myelomonocytic leukaemia

Nature volume 313, pages 709–711 (1985)Cite this article

Abstract

The metallothioneins (MTs) are a family of proteins of low relative molecular mass which bind heavy-metal ions1. MTs exist in several molecular forms (MT-I, MT-II) and are encoded by a multi-gene family containing at least 14 closely related genes and pseudogenes1,2. These proteins function in the regulation of trace-metal metabolism, the storage of these ions in the liver, and as a protective mechanism against heavy-metal toxicity3. Somatic cell hybridization has shown that most MT genes, including the functional MT genes (MT1A, MT1B, MT2A), lie on human chromosome 16 (refs 4, 5). Using in situ hybridization6,7, we have now localized the MT genes to band q22 of chromosome 16. This chromosomal band is also a breakpoint in two specific rearrangements, the inv(16)(p13q22) (ref. 8) and t(16; 16)(pl3;q22) rearrangements, found in a subgroup of patients with acute myelomonocytic leukaemia (AMML). Hybridization of a MT probe to malignant cells from two patients with an inv(16) showed labelled sites on both arms of the inverted chromosome, indicating that the breakpoint at 16q22 splits the MT gene cluster. Similar results were obtained when this probe was hybridized to metaphase cells from two patients with a t(16; 16). These results suggest that the MT genes or their regulatory regions9 may function as an ‘activating’ sequence for an as yet unidentified cellular gene located at 16pl3.

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Author notes

  1. Michael Karin: Department of Microbiology, University of Southern California School of Medicine, Los Angeles, California 90033, USA

Authors and Affiliations

  1. Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, 60637, USA

    Michelle M. Le Beau, Manuel O. Diaz, Michael Karin & Janet D. Rowley

Authors
  1. Michelle M. Le Beau
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  2. Manuel O. Diaz
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  3. Michael Karin
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  4. Janet D. Rowley
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Le Beau, M., Diaz, M., Karin, M. et al. Metallothionein gene cluster is split by chromosome 16 rearrangements in myelomonocytic leukaemia. Nature 313, 709–711 (1985). https://doi.org/10.1038/313709a0

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