Comparison of childhood leukemia initiating cell populations in NOD/SCID and NSG mice

Abstract

Leukemia initiating cells (LICs) are defined by their ability to generate leukemias in animal models and to self-renew by repopulating serial recipients. Recent findings suggest that multiple sub-populations of acute leukemia cells are capable of engrafting immune deficient mice raise important questions about the biology of these diseases.1, 2, 3 If several cell populations have LIC properties, what are the relationships of these stem cell populations to each other and which populations are most important to target with therapy? To address these questions, it is crucial to utilize assays that are capable of identifying any leukemia cells that possess stem cell properties. The recently developed NOD/LtSz-scid IL-2Rγc null (NSG) mouse is now considered a more permissive host for the growth and development of normal and acute myeloid leukemia cells than the nonobese diabetic severe combined immune deficient (NOD/SCID) strain.4, 5 In acute lymphoblastic leukemia (ALL) engraftment of high-risk cases has been reported to be slower in NOD/SCID than NSG but otherwise leukemias developed in both strains.6 However, another study reported that engraftment of T-ALL cells was improved using NSG mice.7 Observations that different populations of cells can engraft different mouse strains raise questions as to how the reports that used only NOD/SCID mice should be interpreted. NSG and NOD/SCID strains have not previously been directly and quantitatively compared for engraftment potential of pediatric LIC sub-populations using the same source of cells. Such studies should provide clear information as to the permissiveness of each strain and which sub-populations have LIC potential.