Rag2null/γcnull mice are suitable for long-term in vivo propagation of juvenile myelomonocytic leukemia

Resistance to therapy in juvenile myelomonocytic leukemia (JMML) is to a large extent determined by epigenetic modifications. For better insight into epigenetic processes in JMML-initiating cells we established a xenotransplantation model of primary human JMML cells in Rag2null/γcnull mice. Persistent engraftment of cells from three patients with different PTPN11 leukemia mutations was achieved by intrahepatic injection of 106 cells into newborn mice or intravenous injection of 5 × 106 cells into adult mice. Median infiltration with human CD45+ cells in peripheral blood, bone marrow, spleen and liver was 1%, 27%…