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

Acute leukemias arise secondary to chromosomal aberrations that cause dysfu nctions in gene regulation and regulatory factors. Significant differences in morphology between acute leukemic and non leukemic hematopoietic cells a re readily observed. How morphologic changes of the nuclei of acute leukemi c 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 perturbat ions of gene expression in acute leukemic cells. Using in situ immunofluore scence microscopy, we addressed the interrelationships of modifications in nuclear morphology with the intranuclear distribution of leukemia-related r egulatory factors (including ALL-1, PML, and AF-9) in cells from patients w ith acute leukemia. We compared the localization of leukemia-associated pro teins with various factors involved in gene transcription and RNA processin g (e.g., RNA polymerase II and SC-35). Our findings suggest that there are leukemia-associated aberrations in mechanisms that direct regulatory factor s to sites within the nucleus. This misplacement of key cognate factors may contribute to perturbations in gene expression characteristic of leukemias . J. Cell. Biochem. 77:30-33, 2000. (C) Wiley-Liss, Inc.