| First Author | Wang HC | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 8 | Pages | 114542 |
| PubMed ID | 39046877 | Mgi Jnum | J:353601 |
| Mgi Id | MGI:7716368 | Doi | 10.1016/j.celrep.2024.114542 |
| Citation | Wang HC, et al. (2024) Kmt2c restricts G-CSF-driven HSC mobilization and granulocyte production in a methyltransferase-independent manner. Cell Rep 43(8):114542 |
| abstractText | Granulocyte colony-stimulating factor (G-CSF) is widely used to enhance myeloid recovery after chemotherapy and to mobilize hematopoietic stem cells (HSCs) for transplantation. Unfortunately, through the course of chemotherapy, cancer patients can acquire leukemogenic mutations that cause therapy-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). This raises the question of whether therapeutic G-CSF might potentiate therapy-related MDS/AML by disproportionately stimulating mutant HSCs and other myeloid progenitors. A common mutation in therapy-related MDS/AML involves chromosome 7 deletions that inactivate many tumor suppressor genes, including KMT2C. Here, we show that Kmt2c deletions hypersensitize murine HSCs and myeloid progenitors to G-CSF, as evidenced by increased HSC mobilization and enhanced granulocyte production from granulocyte-monocyte progenitors (GMPs). Furthermore, Kmt2c attenuates the G-CSF response independently from its SET methyltransferase function. Altogether, the data raise concerns that monosomy 7 can hypersensitize progenitors to G-CSF, such that clinical use of G-CSF may amplify the risk of therapy-related MDS/AML. |
