@article{EffenbergerBommertKunzetal.2017,
  author    = {Effenberger, Madlen and Bommert, Kathryn S. and Kunz, Viktoria and Kruk, Jessica and Leich, Ellen and Rudelius, Martina and Bargou, Ralf and Bommert, Kurt},
  title     = {Glutaminase inhibition in multiple myeloma induces apoptosis via MYC degradation},
  series = {Oncotarget},
  volume    = {8},
  journal   = {Oncotarget},
  number    = {49},
  doi       = {10.18632/oncotarget.20691},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170168},
  pages     = {85858-85867},
  year      = {2017},
  abstract  = {Multiple Myeloma (MM) is an incurable hematological malignancy affecting millions of people worldwide. As in all tumor cells both glucose and more recently glutamine have been identified as important for MM cellular metabolism, however there is some dispute as to the role of glutamine in MM cell survival. Here we show that the small molecule inhibitor compound 968 effectively inhibits glutaminase and that this inhibition induces apoptosis in both human multiple myeloma cell lines (HMCLs) and primary patient material. The HMCL U266 which does not express MYC was insensitive to both glutamine removal and compound 968, but ectopic expression of MYC imparted sensitivity. Finally, we show that glutamine depletion is reflected by rapid loss of MYC protein which is independent of MYC transcription and post translational modifications. However, MYC loss is dependent on proteasomal activity, and this loss was paralleled by an equally rapid induction of apoptosis. These findings are in contrast to those of glucose depletion which largely affected rates of proliferation in HMCLs, but had no effects on either MYC expression or viability. Therefore, inhibition of glutaminolysis is effective at inducing apoptosis and thus serves as a possible therapeutic target in MM.},
  language  = {en}
}
@article{WongWinterHartigetal.2014,
  author    = {Wong, David and Winter, Oliver and Hartig, Christina and Siebels, Svenja and Szyska, Martin and Tiburzy, Benjamin and Meng, Lingzhang and Kulkarni, Upasana and F{\"a}hnrich, Anke and Bommert, Kurt and Bargou, Ralf and Berek, Claudia and Van, Trung Chu and Bogen, Bjarne and Jundt, Franziska and Manz, Rudolf Armin},
  title     = {Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {10},
  doi       = {10.1371/journal.pone.0109018},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115269},
  pages     = {e109018},
  year      = {2014},
  abstract  = {Multiple myeloma is a bone marrow plasma cell tumor which is supported by the external growth factors APRIL and IL-6, among others. Recently, we identified eosinophils and megakaryocytes to be functional components of the micro-environmental niches of benign bone marrow plasma cells and to be important local sources of these cytokines. Here, we investigated whether eosinophils and megakaryocytes also support the growth of tumor plasma cells in the MOPC315. BM model for multiple myeloma. As it was shown for benign plasma cells and multiple myeloma cells, IL-6 and APRIL also supported MOPC315. BM cell growth in vitro, IL-5 had no effect. Depletion of eosinophils in vivo by IL-5 blockade led to a reduction of the early myeloma load. Consistent with this, myeloma growth in early stages was retarded in eosinophil-deficient Delta dblGATA-1 mice. Late myeloma stages were unaffected, possibly due to megakaryocytes compensating for the loss of eosinophils, since megakaryocytes were found to be in contact with myeloma cells in vivo and supported myeloma growth in vitro. We conclude that eosinophils and megakaryocytes in the niches for benign bone marrow plasma cells support the growth of malignant plasma cells. Further investigations are required to test whether perturbation of these niches represents a potential strategy for the treatment of multiple myeloma.},
  language  = {en}
}