Modified intranuclear organization of regulatory factors in human acute leukemias: Reversal after treatment

Authors

  • Jeffrey A. Gordon,

    1. Department of Medicine and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655
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  • Shirwin M. Pockwinse,

    1. Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655
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  • F. Marc Stewart,

    1. Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655
    2. Department of Medicine and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655
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  • Peter J. Quesenberry,

    1. Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655
    2. Department of Medicine and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655
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  • Tatsuya Nakamura,

    1. Department of Microbiology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
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  • Carlo M. Croce,

    1. Department of Microbiology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
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  • Jane B. Lian,

    1. Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655
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  • Janet L. Stein,

    1. Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655
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  • André J. van Wijnen,

    1. Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655
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  • Gary S. Stein

    Corresponding author
    1. Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655
    2. Department of Medicine and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655
    • Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, MA.
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Abstract

Acute leukemias arise secondary to chromosomal aberrations that cause dysfunctions in gene regulation and regulatory factors. Significant differences in morphology between acute leukemic and nonleukemic hematopoietic cells are readily observed. How morphologic changes of the nuclei of acute leukemic cells relate to the underlying functional alterations of gene expression is minimally understood. Spatial modifications in the representation and/or organization of regulatory factors may be functionally linked to perturbations of gene expression in acute leukemic cells. Using in situ immunofluorescence microscopy, we addressed the interrelationships of modifications in nuclear morphology with the intranuclear distribution of leukemia-related regulatory factors (including ALL-1, PML, and AF-9) in cells from patients with acute leukemia. We compared the localization of leukemia-associated proteins with various factors involved in gene transcription and RNA processing (e.g., RNA polymerase II and SC-35). Our findings suggest that there are leukemia-associated aberrations in mechanisms that direct regulatory factors to sites within the nucleus. This misplacement of key cognate factors may contribute to perturbations in gene expression characteristic of leukemias. J. Cell. Biochem. 77:30–43, 2000. © 2000 Wiley-Liss, Inc.

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