Simultaneous demonstration of clonal chromosome abnormalities and apoptosis in individual marrow cells in myelodysplastic syndrome.
Bone marrow samples from 18 patients with myelodysplastic syndrome (MDS) with clonal cytogenetic abnormalities were characterized by combining fluorescence in situ hybridization (FISH) with in situ end-labeling (ISEL) or with annexin V staining and flow cytometry (AV/FLOW) to determine the clonal nature of hematopoietic cells undergoing apoptosis in marrow cells. Apoptosis occurred in both normal and clonal cells. However, the proportion of clonal cells identified by FISH among apoptotic cells was lower than the proportion among nonclonal cells in 17 of 18 patients, regardless of whether ISEL or AV/ FLOW was used to identify apoptosis. This technique allows us to identify simultaneously clonality (as determined by FISH) and apoptosis in individual cells and shows that although apoptosis occurs predominantly in residual normal (FISH-negative) cells, a proportion of clonal precursors in MDS marrow also die from programmed cell death. Such a mechanism may be responsible for the generally slow expansion of the clone in MDS.
Li
Xiao
X
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Bryant
C Eileen
CE
Deeg
H Joachim
HJ
D000368:Aged; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology / Q000473:pathology*; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology