A. Raza et al., APOPTOSIS IN BONE-MARROW BIOPSY SAMPLES INVOLVING STROMAL AND HEMATOPOIETIC-CELLS IN 50 PATIENTS WITH MYELODYSPLASTIC SYNDROMES, Blood, 86(1), 1995, pp. 268-276
Cell-cycle kinetics were measured in situ after infusions of iododeoxy
uridine and/or bromodeoxyuridine in 50 patients with myelodysplastic s
yndromes (MDS) and the median labeling index in bone marrow (BM) biops
y samples was 28.6%. Unfortunately, 26 of 50 patients showed that grea
ter than or equal to 75% of hematopoietic cells of all three lineages
were undergoing programmed cell death (PCD) in their biopsy samples as
shown by the in situ end labeling (ISEL) technique. Ten patients had
1/3 and eight had 2/3 ISEL(+) cells. Stromal cells were frequently ISE
L(+) and often S-phase cells were also found to be simultaneously ISEL
(+). Nucleosomal DNA fragments as a ladder in agarose gel were present
in BM aspirates of four patients who showed high ISEL and were absent
in two who had no ISEL staining in biopsy samples, but only when DNA
was extracted after a 4-hour in vitro incubation in complete medium. T
herefore, laddering data confirmed the ISEL findings that the majority
of hematopoietic cells in MDS are in early stages of PCD. We conclude
that extensive intramedullary cell death may explain the paradox of p
ancytopenia despite hypercellular marrows in MDS patients. Investigati
ng approaches that protect against PCD in some MDS subsets would be of
interest. (C) 1995 by The American Society of Hematology.