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Cytogenetic clonality in myelodysplastic syndromes studied with
fluorescence in situ hybridization: lineage, response to growth factor
therapy, and clone expansion
J Anastasi, J Feng, MM Le Beau, RA Larson, JD Rowley and JW Vardiman
Department of Pathology and Medicine, University of Chicago, IL.
Clonality in myelodysplastic syndromes (MDS) has been studied with various
techniques including glucose-6-phosphate dehydrogenase (G6PD) isoenzyme and
cytogenetic analyses, and with molecular techniques such as gene deletion
studies and the analysis of restriction fragment- length polymorphisms
(RFLP) of X-linked genes. In this study, we investigated the use of
fluorescence in situ hybridization (FISH) with a chromosome-specific probe
to examine cytogenetic clonality in peripheral blood (PB) cells from three
patients with MDS. In each case, trisomy 8 was shown by conventional
cytogenetic analysis at the time of the initial diagnosis. By using FISH
with a probe for the centromere of chromosome 8, we identified the trisomy
in individual PB cells from Wright-stained smears. With this technique, we
could determine the cell lineage involved by the trisomy, and through
serial analyses we could assess the response of the clonal and nonclonal
cells to growth-factor therapy, and the expansion of the trisomic clone
over time. In each of the three cases, various proportions of granulocytes,
monocytes, eosinophils, and basophils showed trisomy 8 by FISH analysis. In
none of the cases did we detect trisomy 8 in lymphocytes. By analysis of PB
cells before and during therapy with recombinant granulocyte-macrophage
colony-stimulating factor (GM-CSF), we found that GM-CSF stimulated both
trisomic and disomic cells. During a 1-year period of sequential study, we
detected an abrupt increase in the percentage of trisomic cells in one
patient, a stable percentage in another, and a slowly increasing percentage
in the third. The abrupt increase in the first patient preceded a
transformation to a more acute phase by 2 months. We conclude that FISH
analysis of PB cells of patients with MDS offers an additional approach to
the study of clonality in this disorder. In some cases this analysis may
provide a useful and simple means of assessing response to therapy and
progression of disease.
Volume 81,
Issue 6,
pp. 1580-1585,
03/15/1993
Copyright © 1993 by The American Society of Hematology
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