Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD / analysis
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Antigens, CD / immunology
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Antigens, CD19
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Antigens, Differentiation, B-Lymphocyte / analysis
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Antigens, Differentiation, B-Lymphocyte / immunology
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Chromosome Aberrations / pathology
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Chromosome Disorders
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Chromosomes, Human, Pair 11
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Chromosomes, Human, Pair 4
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Flow Cytometry
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Histocompatibility Antigens / analysis
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Humans
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Immunotherapy
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Immunotoxins / administration & dosage*
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Leukemia, Experimental / genetics
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Leukemia, Experimental / immunology
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Leukemia, Experimental / therapy*
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Leukocyte Common Antigens
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Mice
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Mice, SCID
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N-Glycosyl Hydrolases*
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Neoplasm Transplantation
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Plant Proteins / administration & dosage
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Ribosome Inactivating Proteins, Type 1
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Translocation, Genetic
Substances
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Antigens, CD
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Antigens, CD19
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Antigens, Differentiation, B-Lymphocyte
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Histocompatibility Antigens
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Immunotoxins
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Plant Proteins
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Ribosome Inactivating Proteins, Type 1
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Leukocyte Common Antigens
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N-Glycosyl Hydrolases
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pokeweed antiviral protein