Cell-cycle kinetics were measured in situ after infusions of iododeoxyuridine and/or bormodeoxyuridine in 50 patients with myelodysplastic syndromes (MDS) and the median labeling index in bone marrow (BM) biopsy samples was 28.6%. Unfortunately, 26 of 50 patients showed that > or = 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 ISEL+ 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. Therefore, 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 pancytopenia despite hypercellular marrows in MDS patients. Investigating approaches that protect against PCD in some MDS subsets would be of interest.

No abstract

The need for reproducibility in the classification of acute leukaemia has made it necessary to incorporate information derived from new techniques which have become essential for the study of these disorders. In addition to classic morphology and cytochemistry (FAB proposals), it is necessary to add immunology and cytogenetics (MIC proposals), as well as to investigate further the biological and diagnostic significance of molecular events. As a result of these investigations a new group of leukaemias merit recognition as distinct entities. These include three types of ALL with specific chromosome abnormalities, namely, i) t (9;22), ii) t (4;11) and iii) t (1;19) and four subtypes of AML, i) with minimal differentiation or AML-M0, ii) with basophilic precursors or M2Baso, iii) AML (M4/M5) with t (8;16) and iv) AML with trilineage myelodysplasia. Biphenotypic acute leukaemia constitutes also a distinct entity with features of ALL and AML and represents a malignancy probably affecting multipotent stem cells. We propose an objective evaluation system for biphenotypic leukaemias based on a score in which the various lineage markers are graded according to their known specificity.