Prognostic Significance of Biomarkers of Diffuse Large B-cell Lymphomas / 대한혈액학회지

BACKGROUND: Biomarkers of lymphomas identified by immunostaining of lymphoma tissues were recently found to have a prognostic value for diffuse large B-cell lymphoma (DLBL). Thus, it seems likely that the prognostic prediction of lymphomas might be improved by incorporating biological markers into well known prognostic systems. METHODS: To determine the clinical significance of the biological markers expressed in DLBL, 26 patients, with de novo DLBL, were retrospectively studied at the Chungnam National University Hospital. Archival specimens from the patients were stained with antibodies for the bcl-2, bcl-6, Ki-67, CD 10, IRF-4, Granzyme-B, MHC-II and p16 antigens. Two immunophenotypic patterns of DLBL were identified by the pattern of differentiation; the germinal center (GC, CD10+/-/Bcl-6+/IRF-4-)-like subgroup and the post germinal center (pGC, CD10+/-/bcl-6+/-/IRF4+)-like subgroup. RESULTS: The median age of the subjects was 56 years, ranging form 37 to 69. After a median follow up duration of 48 months, the median survival time was 44 month, ranging from 1~100 months. The five-year overall survival rate Using the Kaplan-Meier method was 32%. The only biomarker affecting the survival was bcl-2 (P=0.009). The survival of the GC-like subgroup was superior to that of the pGC-like subgroup, but without statistical significance (P=0.064). Among 18 patients with IPI scores 0~2, those expressing bcl-2 (P=0.002) and the pGC-like subgroup had a worse prognosis compared to the GC-like subgroup (P=0.049). CONCLUSION: The prognostic assessment of DLBL patients might be improved by the addition of immunohistochemical profiles, especially for bcl-2, to the traditional IPI system.

Ex vivo Expansion of Hematopoietic Progenitor Cells in Co-culture of Cord Blood CD34+Cells with Human Umbilical Vein Endothelial Cells / 대한혈액학회지

BACKGROUND: We examined an ex vivo expansion system for cord blood (CB) hematopoietic progenitor cells, which is based upon a co-culture of CD34+cells with human umbilical endothelial cells (HUVECs) in the presence of stromal cell-derived factor-1 (SDF-1) and hematopoietic growth factors. METHODS: Cord blood CD34+cells were either incubated a liquid suspension culture or co-cultured on HUVEC monolayers with hematopoietic growth factors in the presence or absence of SDF-1. After 7~14 days of culture, cells were harvested and analyzed for fold-increase in nucleated cells, CD34+ cells, and colony-forming cells (CFCs) and apoptosis. RESULTS: Seven-day suspension culture of CD34+ cells in the presence of a cytokine combination consisting of throbmopoietin, flk-2 ligand, and kit-ligand (TFK) led to a 43-fold increase of nucleated cells, a 19-fold increase of CD34+ cells, and 14-fold increase of CFCs, respectively. The addition of SDF-1 to TFK slightly further increased this expansion. A co-culture of CD34+ cells with HUVECs significantly enhanced the expansion of both CD34+ cells and CFCs compared with a liquid suspension culture. This was further increased by the addition of SDF-1. A co-culture of CD34+ cells on HUVECs transfected with null-adenoviral vector led to a better fold increase of haemtopoietic progenitor cells compared with a culture with non-transfected HUVECs. Adding SDF-1 to the co-culture diminished the annexn V-positive cells both in the supernatant and adherent cell layers. CONCLUSION: A co-culture of cord blood cells with HUVECs in the presence of hematopoietic growth factors and SDF-1 could be a new model for the efficient expansion of hematopoietic progenitors.