Growth and biologic properties of karyotypically defined subcategories of adult acute lymphocytic leukemia in mice with severe combined immunodeficiency

Abstract

Modest progress has been achieved over the past two decades in the treatment of adult acute lymphocytic leukemia (ALL). With modern therapy, response rates are 70% to 80%, but cure rates only average 25% to 30%. Improved in vivo models are needed to investigate the biology of adult ALL and to test new treatment concepts. Fresh leukemia samples from children with ALL have been successfully transplanted into mice with severe combined immunodeficiency (SCID), but no experience exists for adult ALL. We treated SCID mice with 2 mg cyclophosphamide 24 hours before intravenously injecting 20 x 10(6) viable leukemia cells obtained from 13 patients with newly diagnosed adult ALL within five defined phenotype/karyotype subcategories. Ten (76%) of 13 injected leukemia specimens representing all five categories engrafted. The median survival duration of mice was 20 weeks from the time of leukemia cell injection. The rate of engraftment by ALL subset was as follows: two of two T-cell, two of three t(11q23), two of two hyperdiploid, two of three t(9;22), and two of three diploid ALL. The pattern of organ involvement by leukemia in the mice was similar to that of the human disease. Immunohistochemistry and flow cytometry documented the stability of each leukemic phenotype after passage through SCID mice. Cells transplanted from the spleen and bone marrow of mice engrafted with ALL into recipient mice resulted in consistent engraftment. The survival duration in passage groups was similar to that in groups injected with primary cells. The high frequency of engraftment, availability of frozen original specimens, and successful passages in SCID mice provide an in vivo model of adult ALL suitable for further studies of the disease biology and for design of drug studies for the different subtypes of previously untreated adult ALL.