Detection of monosomy 7 in interphase cells of patients with myeloid disorders

Six patients, five with acute myeloid leukemia (AML) and one with a
myelodysplastic syndrome (MDS), were found to have monosomy 7 by
conventional cytogenetics at diagnosis. Repetitive DNA sequences
from the heterochromatic region of human chromosomes 1 and 7 were
used as probes for in situ hybridization experiments on interphase
cells of these patients. A double hybridization protocol was used
to reveal the particular chromosomes as distinct spots or clusters
of signals within interphase nuclei. The chromosome 1 sequence
served as an internal control. Simultaneous detection of the
sequences showed the presence of two normal number 1 chromosomes
and a missing 7 chromosome from individual cells. While cytogenetic
preparations showed only -7 metaphases in 3 AML and 1 MDS patients,
in situ hybridization of interphase cells showed many normal cells
as well as the presence of -7 in fully mature granulocytes. One AML
patient studied in remission showed only normal metaphases yet had
9% interphase cells with a missing 7 and relapsed within 3 months.
We conclude that examination of interphase cells by in situ
hybridization provides clinically useful data since every cell
including mature granulocytes can be examined, the lineage of a
cell can be determined, and efficacy of differentiation therapy can
be evaluated.