Abnormally High Levels of Circulating CD34+CD38−, CD34+CD38+, and CD10+ Hematopoietic Stem and Progenitor Cells in the Peripheral Blood of B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients Suggest the Presence of Additional Therapeutic Target Cells.

Abstract

Chronic Lymphocytic Leukemia (CLL) is a lymphoproliferative disorder manifested by a clonal expansion of mature long-lived functionally defective lymphocytes that are predominantly of B-cell origin (>95% of cases). CLL cells typically express the pan-B-cell antigens CD19 and CD20 as wells as CD5, an antigen of mature T-cells, which is present in 95% of B-CLL patients and is helpful for diagnosis. The disease has a median survival of 8–10 years. Asymptomatic patients (RAI stages 0–2) are often not treated. RAI stages 3 & 4 are generally treated. Current therapies for CLL included a combination of monoclonal antibodies (anti-CD20 monoclonal antibody, rituximab) with purine analogs (fludarabine or pentostatin) and alkylating agents (cyclophosphamide). Current therapies to manage B-cell CLL are not curative and therefore suggest that the current strategy of targeting therapy against B-cells may leave behind residual disease that contributes to progression or relapse. The importance of more primitive Hematopoietic Stem and Progenitor cell populations in B-CLL patients has not been considered. We hypothesized that circulating cells may be spontaneously mobilized into the periphery of CLL patients and would therefore contribute to the peripheral blood microenvironment. To test this hypothesis we examined existing CLL cell populations from un-treated “watch-and-wait” B-CLL patients as compared to normal volunteer donor peripheral blood cell populations utilizing multivariate flow cytometric analysis. We determined CD34+CD38−, CD34+CD38+, and CD10 levels in normal peripheral blood to be 81.0±14.5, 497.3±78.33, and 83.6±17.5 cells/ml respectively. We report here the presence of abnormally high levels of these stem and progenitor cell populations in B-CLL patients (see table). Although the mechanism behind the release of these cells into the periphery in B-CLL patients is unknown, it is reasonable to propose that they may be contributing to the manifestation of the disease and are therefore potential novel target cell populations for future therapies.B-CLL PatientsWBCβ2mCD34+CD38−CD34+CD38+CD10+7.932.42,52614.623,11911.86U3,14558.21,44912.5U30711.721,77316.93.76,4502513,77117.243.0285.798,02419.371.84,0861808,24719.9U1,79018.63,09919.92U52934.116,03925.811.82,9371944,61731.212.920,75330424,34043.131.51,577260.49281,97673.983.21,0991,76777,525105.532.23,26622024,070White Blood Cell (WBC) counts are expressed as 1x106 cells/ml. All other counts are expressed as cells/ml