Title

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

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Medicine and Cancer Center; Department of Cell Biology

Date

2-19-2000

Document Type

Article

Medical Subject Headings

Cell Nucleus; DNA-Binding Proteins; *Gene Expression Regulation, Neoplastic; Humans; Leukemia; Microscopy, Fluorescence; Myeloid-Lymphoid Leukemia Protein; Neoplasm Proteins; Nuclear Proteins; *Proto-Oncogenes; Transcription Factors; Tumor Cells, Cultured; Tumor Suppressor Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: J Cell Biochem. 2000 Feb;77(1):30-43.

Related Resources

Link to article in PubMed

PubMed ID

10679814