Growth and biologic properties of karyotypically defined subcategories of
adult acute lymphocytic leukemia in mice with severe combined
immunodeficiency
S Jeha, H Kantarjian, S O'Brien, Y Huh, P Pisa, N Ordonez and M Beran
Department of Pediatrics, University of Texas M.D. Anderson Cancer Center,
Houston 77030, USA.
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.
Volume 86,
Issue 11,
pp. 4278-4285,
12/01/1995
Copyright © 1995 by The American Society of Hematology