| First Author | Zhang D | Year | 2021 |
| Journal | Cell Death Dis | Volume | 12 |
| Issue | 5 | Pages | 495 |
| PubMed ID | 33993198 | Mgi Jnum | J:329693 |
| Mgi Id | MGI:6812450 | Doi | 10.1038/s41419-021-03748-y |
| Citation | Zhang D, et al. (2021) BMI1 regulates multiple myeloma-associated macrophage's pro-myeloma functions. Cell Death Dis 12(5):495 |
| abstractText | Multiple myeloma (MM) is an aggressive malignancy characterized by terminally differentiated plasma cells accumulation in the bone marrow (BM). MM BM exhibits elevated MPhis (macrophages) numbers relative to healthy BM. Current evidence indicates that MM-MPhis (MM-associated macrophages) have pro-myeloma functions, and BM MM-MPhis numbers negatively correlate with patient survival. Here, we found that BMI1, a polycomb-group protein, modulates the pro-myeloma functions of MM-MPhis, which expressed higher BMI1 levels relative to normal MPhis. In the MM tumor microenvironment, hedgehog signaling in MPhis was activated by MM-derived sonic hedgehog, and BMI1 transcription subsequently activated by c-Myc. Relative to wild-type MM-MPhis, BMI1-KO (BMI1 knockout) MM-MPhis from BM cells of BMI1-KO mice exhibited reduced proliferation and suppressed expression of angiogenic factors. Additionally, BMI1-KO MM-MPhis lost their ability to protect MM cells from chemotherapy-induced cell death. In vivo analysis showed that relative to wild-type MM-MPhis, BMI1-KO MM-MPhis lost their pro-myeloma effects. Together, our data show that BMI1 mediates the pro-myeloma functions of MM-MPhis. |
