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ADP dependent glucokinase as a novel onco-target for haematological malignancies.

Tandon, Amol

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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.

Item Type: Dissertation
Supervisor: Sauer, PD Dr. Sven
Place of Publication: Heidelberg, Germany
Date of thesis defense: 21 November 2018
Date Deposited: 21 Dec 2018 09:33
Date: 2018
Faculties / Institutes: The Faculty of Bio Sciences > Dean's Office of the Faculty of Bio Sciences
Subjects: 500 Natural sciences and mathematics
570 Life sciences
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