Intramedullary Apoptosis Of Hematopoietic Cells In Myelodysplastic Syndrome Patients Can Be Massive: Apoptotic Cells Recovered From High-Density Fraction Of Bone Marrow Aspirates

A higher percentage of apoptotic cells (apoptotic index or Al) is consistently found in bone marrow (BM) biopsies compared to BM aspirates of patients with myelodysplastic syndrome (MDS). Most studies have only investigated the low-density fraction (LDF) mononuclear cells from BM aspirates following density separation for Al determination, In the present study, both LDF and high-density fraction (HDF) cells for Al were examined by electron microscopy (EM) in 10 MDS patients and 4 healthy donors, Matched BM biopsies were subjected to Al detection by in situ end labeling (ISEL) of fragmented DNA, The results indicate that in LDF and HDF cells, Al is consistently higher in MDS patients (8.5% vs 1.5%, respectively; P=.039) compared to healthy donors (27% vs 4%, respectively; P=.004). The BM biopsy Al was also higher in MDS patients than in healthy donors (3+ vs 0+, respectively; P =.036). In addition, in MDS patients, more apoptotic cells were found in HDF cells than in LDF cells (27% vs 8.5%, respectively; P=.0001). All stages of maturation, ranging from blasts to terminally mature cells belonging to all 3 lineages, were represented in the dying cells in both compartments. Using EM, typical Pelger-Huett-type cells appeared to be apoptotic granulocytes. Both LDF and HDF cells should be examined for an accurate estimation of apoptotic cells because Al would be underestimated if only the LDF cells were studied, Ultrastructural studies consistently show a higher Al in BM biopsies compared to BM aspirates despite the correction factor of HDF cells provided by Al, This may represent the actual extant state, which could conceivably be due to a higher concentration of proapoptotic signals in the biopsies. (Blood, 2000;96:1388-1392) (C) 2000 by The American Society of Hematology.