DETECTION OF NUMERICAL ABERRATIONS IN HEMATOLOGIC NEOPLASIAS BY FLUORESCENCE IN-SITU HYBRIDIZATION

Background and Objective. Over the last 5 years, fluorescence in situ hybridization (FISH) techniques have had an important impact on molecu lar cytogenetic diagnosis, providing a better understanding of the rol e of numerical aberrations in hemopoietic neoplasms. The objective of this article is to analyze the clinical applications of FISH in the ma nagement of hemopoietic malignancies. Evidence and Information Sources . The material examined in the present review includes articles and ab stracts published in journals covered by the Science Citation Index(R) and Medline(R), and personal published and unpublished data. State of art. FISH technology has the advantage of being relatively simple, fa st and flexible. Published data and ongoing prospective studies show t hat, under well-controlled experimental conditions, interphase FISH is more sensitive than conventional metaphase analysis in the detection of numerical abnormalities. Due to the relatively high rate of false p ositive results, FISH cannot be used for the study of minimal residual disease. However, since molecular strategies for the detection of sma ll-sized aneuploid clones have not been developed yet, FISH represents a useful adjunct to conventional cytogenetics, especially for the qua ntitation of the size of abnormal clones during the course of the dise ase and to monitor XX/XY chimerism following sex mis-matched bone marr ow transplantation. Different approaches to the study of multiple cell -lineage involvement by chromosome changes have been developed that ta ke advantage of FISH techniques by: a) simultaneous FISH and membrane immunophenotyping of cytologic and histologic preparations; b) two-ste p analysis based on assessment of the morphology of cells on panoptica l stains, with subsequent hybridization and relocation of previously i dentified cells; c) FISH analysis of enriched cell fractions obtained by cell sorting or by separation of bone marrow cells on a density gra dient, and d) study of single hemopoietic colonies grown in semisolid media. Perspectives. New molecular cytogenetic techniques, such as dua l color FISH comparative genomic hybridization, are at hand that will greatly improve the diagnostic power of cytogenetics and make FISH inc reasingly useful in research laboratories as well as in clinical pract ice. (C) 1997, Ferrata Storti Foundation.