| First Author | Chiche J | Year | 2019 |
| Journal | Cell Metab | Volume | 29 |
| Issue | 6 | Pages | 1243-1257.e10 |
| PubMed ID | 30827861 | Mgi Jnum | J:276002 |
| Mgi Id | MGI:6313687 | Doi | 10.1016/j.cmet.2019.02.002 |
| Citation | Chiche J, et al. (2019) GAPDH Expression Predicts the Response to R-CHOP, the Tumor Metabolic Status, and the Response of DLBCL Patients to Metabolic Inhibitors. Cell Metab 29(6):1243-1257.e10 |
| abstractText | Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease treated with anti-CD20-based immuno-chemotherapy (R-CHOP). We identified that low levels of GAPDH predict a poor response to R-CHOP treatment. Importantly, we demonstrated that GAPDH(low) lymphomas use OxPhos metabolism and rely on mTORC1 signaling and glutaminolysis. Consistently, disruptors of OxPhos metabolism (phenformin) or glutaminolysis (L-asparaginase) induce cytotoxic responses in GAPDH(low) B cells and improve GAPDH(low) B cell-lymphoma-bearing mice survival, while they are low or not efficient on GAPDH(high) B cell lymphomas. Ultimately, we selected four GAPDH(low) DLBCL patients, who were refractory to all anti-CD20-based therapies, and targeted DLBCL metabolism using L-asparaginase (K), mTOR inhibitor (T), and metformin (M) (called KTM therapy). Three out of the four patients presented a complete response upon one cycle of KTM. These findings establish that the GAPDH expression level predicts DLBCL patients' response to R-CHOP treatment and their sensitivity to specific metabolic inhibitors. |
