Arginine dependency is a therapeutically exploitable vulnerability in chronic myeloid leukaemic stem cells.

ABSTRACT: To fuel accelerated proliferation, leukaemic cells undergo metabolic deregulation, which can result in specific nutrient dependencies. Here, we perform an amino acid drop-out screen and apply pre-clinical models of chronic phase chronic myeloid leukaemia (CML) to identify arginine as a nutrient essential for primary human CML cells. Analysis of the Microarray Innovations in Leukaemia (MILE) dataset uncovers reduced ASS1 levels in CML compared to most other leukaemia types. Stable isotope tracing reveals repressed activity of all urea cycle enzymes in patient-derived CML CD34⁺ cells, rendering them arginine auxotrophic. Thus, arginine deprivation completely blocks proliferation of CML CD34⁺ cells and induces significantly higher levels of apoptosis when compared to arg

SUBMITTER: Rattigan KM 

PROVIDER: S-EPMC10561355 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature