Interphase cytogenetic analysis of in vivo differentiation in the
myelodysplasia of Down syndrome
A Zipursky, H Wang, EJ Brown and J Squire
Department of Pediatrics, Hospital for Sick Children, Toronto, Canada.
In Down syndrome, acute megakaryoblastic leukemia (AMKL) occurs frequently
during the first 4 years of life and is usually preceded by a period of
myelodysplasia (MDS), often associated with chromosomal abnormalities.
Archival peripheral blood and/or bone marrow films of six patients with
Down syndrome and MDS whose leukemic cells contained monosomy 7 or trisomy
8 were studied to determine whether the abnormal precursors produce mature
cells in vivo. Using fluorescence in situ hybridization (FISH) of
interphase nuclei with chromosome-specific centromere probes for either
chromosome 7 or 8, we were able to determine which cells had one, two, or
three signals indicative of one, two, or three no. 7 or 8 chromosomes. In
five patients with trisomy 8, 80% to 100% (94.5% +/- 6.2%) of the
megakaryoblasts had three signals using a chromosome 8 probe; in one
patient with monosomy 7, 96.5% of the megakaryoblasts had one signal using
a chromosome 7 probe. In all six patients, the myeloid and lymphoid series
did not have evidence of the chromosomal abnormality present in the blasts.
In three of five patients with trisomy 8, three signals were observed in
27%, 33%, and 41% of normoblasts, respectively. These data are evidence
that the abnormal cell in MDS is a progenitor cell with the potential of
forming cells of megakaryocyte and erythroid lineages.
Volume 84,
Issue 7,
pp. 2278-2282,
10/01/1994
Copyright © 1994 by The American Society of Hematology
