title: Human acute leukemia cells injected in NOD/LtSz-scid/IL-2Rgamma null mice generate a faster and more efficient disease compared to other NOD/scid-related strains.
abstract: Transplantation of human acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) primary cells and cell lines in different strains of immunodeficient mice has led to preclinical models extensively used to investigate acute leukemia stem cells, biology and drug sensitivity. We studied the engraftment kinetics of AML and ALL cell lines and primary cells in 3 strains of NOD.CB17-Prkdc(scid) (NOD/scid, NS)-related mice (NOD.Cg-Prkdc(scid)B2m(tm1Unc)/J, abbreviated NOD/scid/beta2 null, NSB; and NOD.Cg-Prkdc(scid)Il2rg(tm1Wjll)/SzJ, abbreviated NOD/scid/IL-2Rgamma null, NSG). The engraftment of human malignant cells was investigated by means of clinicopathological criteria, flow cytometry, PCR and immunohistochemistry. In NSG mice, we observed a significantly faster development of leukemia-related symptoms and a higher percentage of leukemia cells in the blood, in the marrow and in the spleen. The leukemia-related angiogenic switch (measured as the number of circulating endothelial cells and progenitors) was faster in NSG compared to NS and NSB mice. These models will be instrumental to studies on leukemia-initiating stem cells, leukemia biology, preclinical treatment studies, and to obtain patient-specific preclinical models to design and investigate patient-tailored therapies.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, European Institute of Oncology, Milan, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Agliano
authors.forename: Ines
authors.initials: I
authors.lastname: Martin-Padura
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mancuso
authors.forename: Paola
authors.initials: P
authors.lastname: Marighetti
authors.forename: Cristina
authors.initials: C
authors.lastname: Rabascio
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pruneri
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000502:physiology*; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit