title: Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome.
abstract: Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal stem-cell disorders characterized by ineffective hematopoiesis and risk of progression to acute myeloid leukemia. Increased apoptosis and suppressed functions of peripheral blood natural killer (NK) cells have been described in MDS patients, but only limited information is available on the phenotypic and functional integrity of NK cells in the bone marrow. In a cohort of 41 patients with distinct clinical subtypes of MDS, we here show that NK cells in the bone marrow show decreased surface expression of the activating receptors DNAM-1 and NKG2D. Notably, decreased receptor expression correlated with elevated bone marrow blast counts and was associated with impaired NK-cell responsiveness to stimulation with the K562 cell line, or co-activation by NKG2D or DNAM-1 in combination with the 2B4 receptor. Furthermore, antibody-masking experiments revealed a central role for DNAM-1 in NK cell-mediated killing of freshly isolated MDS blasts. Thus, given the emerging evidence for NK cell-mediated immune surveillance of neoplastic cells, we speculate that reduced expression of DNAM-1 on bone marrow NK cells may facilitate disease progression in patients with MDS.
authors.affiliation: Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. mattias.carlsten@ki.se
authors.forename: M
authors.initials: M
authors.lastname: Carlsten
authors.forename: B C
authors.initials: BC
authors.lastname: Baumann
authors.forename: M
authors.initials: M
authors.lastname: Simonsson
authors.forename: M
authors.initials: M
authors.lastname: Jädersten
authors.forename: A-M
authors.initials: AM
authors.lastname: Forsblom
authors.forename: C
authors.initials: C
authors.lastname: Hammarstedt
authors.forename: Y T
authors.initials: YT
authors.lastname: Bryceson
authors.forename: H-G
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: E
authors.initials: E
authors.lastname: Hellström-Lindberg
authors.forename: K-J
authors.initials: KJ
authors.lastname: Malmberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D018952:Antigens, CD34; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1