| First Author | Villatoro A | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 12 |
| PubMed ID | 36596811 | Mgi Jnum | J:340917 |
| Mgi Id | MGI:7424251 | Doi | 10.1038/s41467-022-35700-9 |
| Citation | Villatoro A, et al. (2023) Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation. Nat Commun 14(1):12 |
| abstractText | Here we explored the role of interleukin-1beta (IL-1beta) repressor cytokine, IL-1 receptor antagonist (IL-1rn), in both healthy and abnormal hematopoiesis. Low IL-1RN is frequent in acute myeloid leukemia (AML) patients and represents a prognostic marker of reduced survival. Treatments with IL-1RN and the IL-1beta monoclonal antibody canakinumab reduce the expansion of leukemic cells, including CD34(+) progenitors, in AML xenografts. In vivo deletion of IL-1rn induces hematopoietic stem cell (HSC) differentiation into the myeloid lineage and hampers B cell development via transcriptional activation of myeloid differentiation pathways dependent on NFkappaB. Low IL-1rn is present in an experimental model of pre-leukemic myelopoiesis, and IL-1rn deletion promotes myeloproliferation, which relies on the bone marrow hematopoietic and stromal compartments. Conversely, IL-1rn protects against pre-leukemic myelopoiesis. Our data reveal that HSC differentiation is controlled by balanced IL-1beta/IL-1rn levels under steady-state, and that loss of repression of IL-1beta signaling may underlie pre-leukemic lesion and AML progression. |
