Leukemia cells invading the liver express liver chemokine receptors and possess characteristics of leukemia stem cells in mice with MPD-like myeloid leukemia

ObjectiveMassive liver infiltration by leukemic cells is an indicator of poor prognosis in some hemoblastoses. The aim of this study was to determine the mechanism of liver invasion by leukemic cells using the mouse model of transplantable myeloproliferative disease-like myeloid leukemia characterized by liver invasion.Materials and MethodsCD45+ cells from the liver of mice transplanted with leukemic cells were sorted by magnetic separation. Gene expression alterations in CD45+ cells invading the liver were examined by polymerase chain reaction arrays and quantitative real-time polymerase chain reaction (including polymerase chain reaction arrays) analysis of selected genes.ResultsLiver chemokine receptors (Ccr1, Ccr2, Ccr5, and others) were expressed in cells invading the liver. The expression level of Ccr1 was increased 149-fold in comparison with CD45+ cells derived from the livers of healthy mice. Expression levels of several genes responsible for proliferation and self-renewal were elevated dramatically, which is in accordance with a high concentration of leukemia stem cells in the livers of moribund animals. The nuclear factor−κB signaling pathway and several oncogenes are also activated in these leukemia cells.ConclusionsOverexpression of liver-specific cytokine receptors allowed the leukemic cells to invade the liver. The high concentration of leukemia stem cells in the liver suggests the cells of this leukemia are able to adapt to new extramedullar niches. The model for the investigation and development of preventative strategies against massive liver invasion are described here.