| First Author | Agarwal P | Year | 2021 |
| Journal | Cell Rep | Volume | 36 |
| Issue | 2 | Pages | 109386 |
| PubMed ID | 34260914 | Mgi Jnum | J:330750 |
| Mgi Id | MGI:6874565 | Doi | 10.1016/j.celrep.2021.109386 |
| Citation | Agarwal P, et al. (2021) TNF-alpha-induced alterations in stromal progenitors enhance leukemic stem cell growth via CXCR2 signaling. Cell Rep 36(2):109386 |
| abstractText | Chronic myeloid leukemia (CML) is propagated by leukemia stem cells (LSCs) that are not eradicated by tyrosine kinase inhibitor (TKI) treatment and persist as a source of disease recurrence. Bone marrow (BM) mesenchymal niches play an essential role in hematopoietic stem cell (HSC) and LSC maintenance. Using a murine CML model, we examine leukemia-induced alterations in mesenchymal cell populations. We show that 6C3+ stromal progenitors expand in CML BM and exhibit increased LSC but reduced HSC supportive capacity. Tumor necrosis factor alpha (TNF-alpha) signaling mediates expansion and higher expression of CXCL1 in CML BM 6C3+ cells and higher expression of the CXCL1 receptor CXCR2 in LSCs. CXCL1 enhances LSC proliferation and self-renewal, whereas CXCR2 inhibition reduces LSC growth and enhances LSC targeting in combination with tyrosine kinase inhibitors (TKIs). We find that TNF-alpha-mediated alterations in CML BM stromal niches enhance support of LSC maintenance and growth via CXCL1-CXCR2 signaling and that CXCR2 inhibition effectively depletes CML LSCs. |
