Cell doi:10.1016/j.cell.2018.02.048 (2018)

Glycolysis generates ATP for cellular energy, whereas shunting glucose into the pentose-phosphate pathway (PPP) is needed to generate the antioxidant NADPH that is necessary for cellular redox balance. In Cell, Müschen and colleagues report that B cells, but not myeloid cells, critically require the phosphatase PP2A to maintain their redox balance and viability by redirecting glucose into the PPP. Loss of PP2A increases that oxidative stress of B lineage cells and, notably, B cell–derived leukemias. B cells normally have low expression of PPP enzymes due to repression of G6pdx and G6pd2 by the transcription factors Pax5 and Ikaros, which makes B cells more sensitive to the activity of PP2A. Patient-derived B cell leukemias and lymphomas also show dependence on the activity of PP2A, which suggests that it might be targeted for therapeutic intervention.