EXCESSIVE PROLIFERATION MATCHED BY EXCESSIVE APOPTOSIS IN MYELODYSPLASTIC SYNDROMES - THE CAUSE-EFFECT RELATIONSHIP

The paradox of pancytopenia despite cellular bone marrows (BM) was inv estigated in 120 patients with myelodysplastic syndromes (MDS). Detail ed cell cycle kinetics were examined following in vivo infusions of io do-and/or bromodeoxyuridine (IUdR/BrdU), while the incidence of apopto sis was measured by in situ end labeling (ISEL) of fragmented DNA. Res ults showed that MDS are highly proliferative disorders with an equall y high incidence of apoptotic intramedullary cell death accounting for the paradox of cellularity/cytopenia. By double-labeling BM biopsy se ctions for ISEL/BrdU we found the peculiar situation of ''signal anton ymy'' where S-phase cells were frequently apoptotic, a phenomenon so f ar only seen in MDS biopsies. The cause-effect relationship of this ex cessive proliferation/apoptosis is discussed at length.