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  • CANCER-PATIENTS  (2)
  • 1
    Keywords: RECEPTOR ; ANGIOGENESIS ; CANCER ; CELLS ; EXPRESSION ; IN-VITRO ; proliferation ; SURVIVAL ; CELL ; Germany ; VITRO ; DIAGNOSIS ; SUPPORT ; SYSTEM ; microarray ; PROTEIN ; PROTEINS ; SAMPLE ; SAMPLES ; cell line ; LINES ; TIME ; PATIENT ; DNA ; CELL-LINES ; STAGE ; microarrays ; PLASMA ; affymetrix ; CELL-LINE ; chemotherapy ; PATHOGENESIS ; PROGNOSTIC-FACTORS ; CANCER-PATIENTS ; PROGNOSTIC FACTORS ; RECEPTORS ; CANCER PATIENTS ; cell lines ; MULTIPLE-MYELOMA ; beta(2)-microglobulin ; HIGH-DOSE CHEMOTHERAPY ; multiple myeloma ; PROGNOSTIC-FACTOR ; LONG ; STAGING SYSTEM ; BONE ; RELEVANCE ; CANDIDATES ; PLASMA-CELLS ; Plasma cells ; A
    Abstract: Pathogenesis of multiple myeloma is associated with an aberrant expression of pro-proliferative, pro-angiogenic and bone-metabolism-modifying factors by malignant plasma cells. Given the frequently long time span from diagnosis of early-stage plasma cell dyscrasias to overt myeloma and the mostly low proliferation rate of malignant plasma cells, we hypothesize these to similarly express a novel class of inhibitory factors of potential prognostic relevance. Bone morphogenic proteins (BMPs) represent possible candidates as they inhibit proliferation, stimulate bone formation and have an effect on the survival of cancer patients. We assessed the expression of BMPs and their receptors by Affymetrix DNA microarrays (n=779) including CD138-purified primary myeloma cell samples (n=635) of previously untreated patients. BMP6 is the only BMP expressed by malignant and normal plasma cells. Its expression is significantly lower in proliferating myeloma cells, myeloma cell lines or plasmablasts. BMP6 significantly inhibits the proliferation of myeloma cell lines, survival of primary myeloma cells and in vitro angiogenesis. A high BMP6 expression in primary myeloma cell samples delineates significantly superior overall survival for patients undergoing high-dose chemotherapy independent of conventional prognostic factors (International Staging System (ISS) stage, beta(2) microglobulin)
    Type of Publication: Journal article published
    PubMed ID: 19718049
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  • 2
    Keywords: PATHOGENESIS ; PROGNOSTIC-FACTORS ; PLASMA ; affymetrix ; CELL-LINE ; chemotherapy ; CELL-LINES ; multiple myeloma ; HIGH-DOSE CHEMOTHERAPY ; CANCER PATIENTS ; RECEPTORS ; PROGNOSTIC FACTORS ; CANCER-PATIENTS ; cell lines ; MULTIPLE-MYELOMA ; CELL ; human ; VITRO ; DIAGNOSIS ; INHIBITION ; IN-VITRO ; proliferation ; SURVIVAL ; CANCER ; CELLS ; EXPRESSION ; RECEPTOR ; ANGIOGENESIS ; APOPTOSIS ; PATIENT ; LINES ; TRANSPLANTATION ; INDUCTION ; IMPACT ; PROTEINS ; PROTEIN ; SAMPLE ; SAMPLES ; cell line ; BONE ; RELEVANCE ; STEM-CELL ; methods ; PROGNOSTIC-FACTOR ; PLASMA-CELLS ; CANDIDATES ; A ; D ; Plasma cells ; autologous ; WELL
    Abstract: Introduction:Pathogenesis of multiple myeloma is associated with an aberrant expression of pro-proliferative-, pro-angiogenic and bone-metabolism modifying factors by malignant plasma cells. Given the timespan from diagnosis of early-stage plasma cell dyscrasias to overt myeloma and the low proliferation rate of malignant plasma cells, we hypothesize these likewise to express a novel class of inhibitory factors of potential prognostic relevance. Bone morphogenic proteins (BMPs) represent possible candidates as they inhibit proliferation, stimulate bone formation, and have impact on the survival of cancer patients.Methods.We assessed expression of BMPs and their receptors by Affymetrix DNA-microarrays (n=434) including CD138-purified primary myeloma cell samples (n=233) of previously untreated patients treated with high-dose chemotherapy and autologous stem cell transplantation. Inhibition of proliferation of human myeloma cell lines (n=10) and apoptosis induction in primary myeloma cell samples (n=5) is assessed. The inhibition of vitro tubule formation by BMP6 is investigated using the AngioKit-assay.Results.BMP6 is the only BMP expressed by malignant or normal plasma cells. Its expression is significantly lower in proliferating myeloma cells, myeloma cell lines, or plasmablasts. BMP6 significantly inhibits proliferation of myeloma cell lines, survival of primary myeloma cells, and in vitro angiogenesis. High BMP6-expression in primary myeloma cell samples delineates significantly superior overall survival for patients undergoing high-dose chemotherapy independent of conventional prognostic factors (ISS-stage, serum-ß2-microglobulin).Conclusion.BMP6 exemplifies a novel class of factors independently prognostic for overall survival expressed by normal as well as malignant plasma cells that inhibits proliferation of myeloma cells and induction of angiogenesis.Gemeinsame Jahrestagung der Deutschen, Österreichischen und Schweizerischen Gesellschaften für Hämatologie und Onkologie, 2.-6. Oktober 2009, Heidelberg/Mannheim
    Type of Publication: Meeting abstract published
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