Interferon-Alpha Restores the Deficient Expression of the Cytoadhesion Molecule Lymphocyte Function Antigen-3 by Chronic Myelogenous Leukemia Progenitor Cells

Hematopoietic cells from the malignant clone in chronic my-elogenous leukemia (CML) maintain and expand a prolifera-tive advantage over normal hematopoietic cells within the bone marrow. This advantage is often ameliorated or reversed in vivo by IFNa. Based upon earlier studies suggesting decreased adhe-siveness ofCML progenitor cells, we asked whetherCML pro-genitor cells are deficient in their expression of the cytoadhe-sion molecule lymphocyte function antigen-3 (LFA-3, CD58) which is normally expressed on hematopoietic progenitors. Progenitor cells from untreated CML patients showed greatly reduced or absent LFA-3 expression, whereas progenitors from patients treated with IFNa in vivo or in vitro expressed surface LFA-3 at more normal levels. LFA-3-deficient CML progeni-tor cells were unable to stimulate normal regulatory prolifera-tive responses in autologous T cells. We hypothesize that IFNa-sensitive LFA-3 deficiency reflects a cell surface cytoad-hesion defect which may help explain adhesive abnormalities of CML progenitor cells in vitro and clonal proliferation in vivo. (J. Clin. Invest. 1991. 88:2131-2136.) Key words: adhesion-clonal expansion * stem cel