Image-based RNA interference screening reveals an individual dependence of acute lymphoblastic leukemia on stromal cysteine support.

ABSTRACT: Interactions with the bone marrow microenvironment are essential for leukemia survival and disease progression. We developed an imaging-based RNAi platform to identify protective cues from bone marrow derived mesenchymal stromal cells (MSC) that promote survival of primary acute lymphoblastic leukemia (ALL) cells. Using a candidate gene approach, we detected distinct responses of individual ALL cases to RNA interference with stromal targets. The strongest effects were observed when interfering with solute carrier family 3 member 2 (SLC3A2) expression, which forms the cystine transporter xc- when associated with SLC7A11. Import of cystine and metabolism to cysteine by stromal cells provides the limiting substrate to generate and maintain glutathione in ALL. This metabolic interaction reduce

SUBMITTER: Boutter J 

PROVIDER: S-EPMC4294362 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature