Clin. Lab. Haem.
1997, 19, 33–38
Application of the multi-colour FISH to interphase
nuclei and metaphase spreads for simultaneous
examination of monosomy 7 and trisomies 8 and
11 in acute myelocytic leukaemia (AML)
H. ACAR Department of Medical Genetics, University of Selc ¸uk,
A. ACAR Konya, Turkey
Summary We have used the multi-colour (three) fluorescence in situ hybridization (FISH) technique
based on the ratio labelling for the detection of monosomy 7 and trisomies 8 and 11 in 13
cases of acute myeloid leukaemia (AML). Two out of the 13 AML cases showed monosomy
7 and two out of the remaining cases exhibited trisomy 8 in interphase nuclei. Three of
these results were confirmed by metaphase-FISH study. Trisomy 11 was not found either by
the interphase FISH study or in the metaphase FISH study. These results demonstrate the
potential power of multi-colour FISH using ratio labelling to produce more fluorescein colour
in interphase nuclei for the detection of aneuploidies in leukaemia.
Keywords Acute myeloid leukaemia, fluorescence in situ hybridization, monosomy 7, trisomy 8 and
trisomy 11
Introduction philic lineage, which might therefore be a multi-potential
myeloid progenitor cell (Baranger et al. 1990; Kwong et al.
Acute myeloid leukaemia (AML) is a malignant disease
1994). This abnormality observed in AML is seen whether
which affects immature or undifferentiated myeloid cells
alone or as part of a complex karyotype is regarded as
and is characterized by their accumulation in bone marrow
having a poor prognosis. As for trisomy 11, it is a rare
and peripheral blood. Aneuploidy in AML may involve
abnormality although it is a consistent finding in AML.
monosomy 7 and trisomies 8 and 11(Potter et al. 1992).
However, whether alone or with other changes, trisomy
Chromosome 8 trisomy is the most frequent and wide-
11 strongly indicates myeloid disease (Potter et al. 1992).
spread abnormality in AML, MDS and other human malig-
Classical cytogenetic techniques have been extremely
nancies (Yunis 1990). This trisomy appears to be relatively
valuable in detecting these abnormalities, but insufficient
specific for myeloid disorders although it is very rare in
metaphases and/or poor chromosome morphology are very
lymphoid conditions (Anastasi et al. 1993; Nguyen et al.
common problems and leukaemic cells may predominantly
1994). This trisomy is sometimes the sole abnormality or
consist of cells in interphase (Heerema et al. 1993). This
may occur with other chromosomal abnormalities (Sand-
may lead to an underestimation of the size of the malignant
berg 1990). Patients with trisomy 8 usually proceed
clone if only metaphases are investigated. Recently flu-
through a myelodysplastic pre-leukaemic phase before
orescence in situ hybridization (FISH) of interphase nuclei
developing full-fledged AML (Heim et al. 1987). Lack of
and metaphase spreads using chromosome specific DNA
specificity suggests a role in disease progression rather than
probes has been proposed as an alternative to conventional
a causative role. Another frequent change is loss of chro-
cytogenetic techniques. By modifying the FISH technique,
mosome 7. This abnormality is a marker of an abnormal
it has been possible to examine chromosomal abnormalities
clone for bone marrow haematopoietic cells. Monosomy 7
with multi-colour (Arnoldus et al. 1990; Lebo et al. 1991).
is restricted to myeloid disorders mainly AML, MDS and
This system is based on the use of either hapten molecules
also in mature eosinophils, but not in lymphoid conditions
(Nederlof et al. 1989; Nederlof et al. 1990) or the ratio
except in acute Philadelphia (Ph) positive lymphoblastic
labelling system (Dauwerse et al. 1992; Reid et al. 1992)
leukaemia (ALL). This implies that monosomy 7 occurs in
for labelling probes to generate multi-colour FISH. Sim-
a progenitor cell common to the granulocytic and eosino-
ultaneous detection of multiple chromosomes would have
several advantages, such as increased efficiency, smaller
Accepted for publication 24 April 1996
sample requirements, and potential for analysis of larger
Correspondence: Dr H. Acar, Sakarya Mah. Serbetli Sk 10–4, 42080
33
Konya, Tu ¨ rkiye. numbers of chromosomal abnormalities.
© 1997 Blackwell Science Limited