title: Interferon-alpha restores the deficient expression of the cytoadhesion molecule lymphocyte function antigen-3 by chronic myelogenous leukemia progenitor cells.
abstract: Hematopoietic cells from the malignant clone in chronic myelogenous leukemia (CML) maintain and expand a proliferative advantage over normal hematopoietic cells within the bone marrow. This advantage is often ameliorated or reversed in vivo by IFN alpha. Based upon earlier studies suggesting decreased adhesiveness of CML progenitor cells, we asked whether CML progenitor cells are deficient in their expression of the cytoadhesion 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 IFN alpha in vivo or in vitro expressed surface LFA-3 at more normal levels. LFA-3-deficient CML progenitor cells were unable to stimulate normal regulatory proliferative responses in autologous T cells. We hypothesize that IFN alpha-sensitive LFA-3 deficiency reflects a cell surface cytoadhesion defect which may help explain adhesive abnormalities of CML progenitor cells in vitro and clonal proliferation in vivo.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
authors.forename: G
authors.initials: G
authors.lastname: Upadhyaya
authors.forename: S C
authors.initials: SC
authors.lastname: Guba
authors.forename: S A
authors.initials: SA
authors.lastname: Sih
authors.forename: A P
authors.initials: AP
authors.lastname: Feinberg
authors.forename: M
authors.initials: M
authors.lastname: Talpaz
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: A B
authors.initials: AB
authors.lastname: Deisseroth
authors.forename: S G
authors.initials: SG
authors.lastname: Emerson
mesh_terms: D000954:Antigens, Surface / Q000032:analysis*; D001483:Base Sequence; D018968:CD58 Antigens; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000032:analysis*; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D018968:CD58 Antigens; D016898:Interferon-alpha; D008562:Membrane Glycoproteins