L-selectin expression is low on CD34(+) cells from patients with chronic myeloid leukemia and interferon-alpha up-regulates this expression

Background and Objectives. Altered adhesive interaction between bone marrow (BM) stroma and progenitors in chronic myeloid leukemia (CML) may be in pa rt caused by abnormal expression of cell adhesion molecules (CAMs) on malig nant progenitor cells. Treatment of CML with interferon-alpha (IFN-alpha) r e-establishes normal hemopoiesis in some patients in part by restoring norm al adhesive interactions between CML progenitors and BM microenvironment, w hich may in turn be mediated by correcting CAM expression on progenitors. Design and Methods. We investigated the expression of CAMs (L-selectin, bet a(2)-integrin, LFA3, ICAM-1, ICAM-3, NCAM) on purified BM CD34(+) cells fro m CML patients (n = 34) and healthy adults (n = 15) by flow cytometry. Modu lation of L-selectin expression on CD34(+) cells from CML after in vitro tr eatment with IFN-cu was also investigated. Results. The mean percentage of CD34(+) cells expressing L-selectin was sig nificantly lower in CML patients (25.4+/-12.8%) than in normal controls (68 .7+/-8.3%, n=15). CD34(+)/HLA-DR-/low and CD34(+)/ CD38(-/low) co-expressin g L-selectin were also significantly lower in untreated CML (27.4+/-21.8% a nd 39.8+/-26.7%, respectively, n=8) than in controls (61+/-17% and 83.7+/-1 0%, respectively, n=7). In vitro treatment with IFN-alpha of purified CD34( +) BM cells from untreated CML patients (n=8) induced a significant, dose a nd time-dependent increase in the L-selectin expression as indicated by FAG S analysis. Interpretation and Conclusions. We hypothesize that this L-selectin deficie ncy reflects a cell surface adhesion defect of progenitors from CML that is partially restored by in vitro IFN-alpha treatment. These data may help to explain the adhesive abnormalities of CML progenitors to the BM microenvir onment and the In vitro restoration of adhesion capacity after IFN-alpha tr eatment. (C) 2000, Ferrata Storti Foundation.