Establishment of a human t(4;11) leukemia in severe combined immunodeficient mice and successful treatment using anti-CD19 (B43)-pokeweed antiviral protein immunotoxin.
Human acute leukemia, with a chromosomal translocation involving chromosomes 4 and 11, t(4;11)(q21;q23), is the most common form of leukemia in infants and responds very poorly to conventional therapy. A human CD19+ mixed-lineage leukemia cell line with a t(4;11)(q21;q23) translocation, RS4;11, disseminated and proliferated in the hematopoietic tissues and other organs of mice with severe combined immunodeficiency in a manner similar to that observed in humans and killed 100% of the animals. The anti-CD19(B43)-pokeweed antiviral protein immunotoxin selectively inhibited clonogenic RS4;11 cells in vitro, markedly reduced the burden of disseminated leukemia of severe combined immunodeficient mice, and, most importantly, resulted in the long-term survival of treated animals. This severe combined immunodeficient mouse model should be useful for the design of more effective treatment strategies for refractory human leukemias.
Jansen
B
B
Department of Laboratory Medicine/Pathology, University of Minnesota, Minneapolis 55455.
Uckun
F M
FM
Jaszcz
W B
WB
Kersey
J H
JH
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis / Q000276:immunology; D002869:Chromosome Aberrations / Q000473:pathology; D025063:Chromosome Disorders; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000032:analysis; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000008:administration & dosage*; D007942:Leukemia, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D017493:Leukocyte Common Antigens; D051379:Mice; D016513:Mice, SCID; D009699:N-Glycosyl Hydrolases; D009368:Neoplasm Transplantation; D010940:Plant Proteins / Q000008:administration & dosage; D054789:Ribosome Inactivating Proteins, Type 1; D014178:Translocation, Genetic
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D006649:Histocompatibility Antigens; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D017493:Leukocyte Common Antigens; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein