title: ADP dependent glucokinase as a novel onco-target for haematological malignancies. creator: Tandon, Amol subject: 500 subject: 500 Natural sciences and mathematics subject: 570 subject: 570 Life sciences description: In this study we aimed at studying the tumor aggressiveness and differentiation potential of Ramos Burkitt’s lymphoma cells upon mitogenic stimulation in light of a novel regulator of immune cell metabolism and activation, ADPGK. We have identified the role of ADPGK in regulation of aerobic glycolysis in Burkitt’s Lymphoma cells and shown that its knock-out leads to reduced tumor aggressiveness, as measured in-vitro via co-culture, migration experiments and metabolic profile, and in-vivo Zebrafish. We found significantly reduced MYC transcription in ADPGK knock-out Burkitt’s lymphoma cells and importantly, several folds reduction in accumulated random mutations in translocated MYC in these cells. We additionally observed a stalled pathway to differentiation of ADPGK knock out B-cells into plasma cells upon stimulation by mitogenic signals. Overall, the study provided the first insights into the role of a novel ER resident protein acting as a regulator of two complementary phenomenon, cell-differentiation and cancer aggressiveness, and thereby opens up new possibilities of therapeutic interventions for hematopoietic malignancies. date: 2018 type: Dissertation type: info:eu-repo/semantics/doctoralThesis type: NonPeerReviewed format: application/pdf identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/25779/1/Amol_PhD%20Thesis.pdf identifier: DOI:10.11588/heidok.00025779 identifier: urn:nbn:de:bsz:16-heidok-257794 identifier: Tandon, Amol (2018) ADP dependent glucokinase as a novel onco-target for haematological malignancies. [Dissertation] relation: https://archiv.ub.uni-heidelberg.de/volltextserver/25779/ rights: info:eu-repo/semantics/openAccess rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html language: eng