IL-1 receptor antagonist prevents bias to myelopoiesis in hematopoietic stem cells and protects from neoplasia

Interleukin-1ß (IL-1ß) drives hematopoietic stem cell (HSC) differentiation into the myeloid lineage, and enhanced IL-1ß signaling plays a key role in hematological malignancies. However, little is known on the role of its endogenous regulatory cytokine, IL-1 receptor antagonist (IL-1rn), on both healthy and malignant hematopoiesis. Here, we show that inflammation through unbalanced IL-1rn is present in the experimental model of acute myeloid leukemia (AML) driven by the NRAS-G12D oncogene. Overall design: Total RNA was isolated from bone marrow (BM) HSC subsets of Mx1-Cre NRAS-G12D mice (IL-1rn-KO, n=3) and NRAS-G12D control (n=3) mic, 6 weeks after pI:pC injection. HSC were FACS sorted and immunophenotypically defined as follows: lin- c-kit+ Sca-1+ (LSK) CD34- Flt3- long term hematopoietic stem cells (LT-HSC), LSK CD34+ Flt3- short term HSC (ST-HSC) and LSK CD34+ Flt3+ multipotent progenitors (MPP). RNA was amplified and prepared for RNA-Seq using the SMART-Seq v4 Ultra Low Input RNA kit (Clontech).