eprintid: 25779 rev_number: 14 eprint_status: archive userid: 4186 dir: disk0/00/02/57/79 datestamp: 2018-12-21 09:33:26 lastmod: 2019-01-31 12:15:12 status_changed: 2018-12-21 09:33:26 type: doctoralThesis metadata_visibility: show creators_name: Tandon, Amol title: ADP dependent glucokinase as a novel onco-target for haematological malignancies. subjects: 500 subjects: 570 divisions: 140001 adv_faculty: af-14 abstract: 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 id_scheme: DOI id_number: 10.11588/heidok.00025779 ppn_swb: 1653770309 own_urn: urn:nbn:de:bsz:16-heidok-257794 date_accepted: 2018-11-21 advisor: HASH(0x556120b21f78) language: eng bibsort: TANDONAMOLADPDEPENDE2018 full_text_status: public place_of_pub: Heidelberg, Germany citation: Tandon, Amol (2018) ADP dependent glucokinase as a novel onco-target for haematological malignancies. [Dissertation] document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/25779/1/Amol_PhD%20Thesis.pdf