Increased cell apoptosis in bone marrow trephine biopsies and immunomagnetically isolated myeloid progenitor cells in patients with chronic idiopathic neutropenia

The frequency of apoptotic cells in bone marrow trephine biopsies and cytospins of immunomagnetically isolated myeloid progenitor cells was determined in 39 patients with chronic idiopathic neutropenia (CIN) and 12 hematologically normal individuals using the in situ end-labeling (ISEL) apoptosis detection method. We found that 66.7% of the patients but none of the normal controls displayed apoptotic cells equal to or higher than 5% of the total mononuclear cells in bone marrow biopsies (p<0.01). In the double stain, we also found that the proportion of apoptotic CD15⁺ myeloid precursor cells did not differ significantly between patients and control subjects, while the proportion of apoptotic CD34⁺ hemopoietic cells could not be estimated with accuracy because of the presence of CD34⁺ endothelial cells. Significantly increased apoptosis was noted in cytospins of immunomagnetically isolated patient CD34⁺ and CD34⁺/CD33⁺ cells but not CD34^-/CD33⁺ cells, compared to the controls (p<0.001, p<0.02 and p>0.05, respectively). These findings confirm and extend our previous observations in flow-cytometric studies of apoptosis in CIN, indicating that increased apoptosis in CIN bone marrow concerns mainly the CD34⁺ and CD34⁺/CD33⁺ progenitor cell compartments. We conclude that the accelerated apoptosis in these compartments may account for the impaired neutrophil production in CIN patients.