Conditions for engraftment of human acute myeloid leukemia (AML) in SCID mice.
Transplantation of human AML into severe combined immunodeficient (SCID) mice provides a useful experimental model but graft failures have been reported. We investigated the influence of a number of factors on the outgrowth of AML in the SCID mouse bone marrow (BM). The transplantation route and total body irradiation (TBI) were examined using the cell line HL-60 as a model for AML. The role of graft size and recombinant human IL-3 (IL-3) were investigated with patient samples of AML cells. Intravenous transplantation was demonstrated to be superior to intraperitoneal transplantation. Pretransplant conditioning resulted in a dose-dependent increase of AML growth in the SCID mouse. Cell dose titrations ranging from 3 x 10(7) - 3.6 x 10(5) AML cells i.v. per mouse revealed a minimum of 1.1 x 10(6) required for reproducible engraftment. Earlier and more extensive infiltration by human AML cells was seen following injection of greater cell numbers. IL-3 given post-transplantation SCID mouse recipients, promoted AML growth in three cases, whereas a fourth AML cell specimen also grew without support of IL-3. In vitro growth factor responsiveness of AML cells to IL-3 did not predict IL-3 dependence of AML growth in vivo.
Terpstra
W
W
Institute of Hematology, Erasmus University, Rotterdam, The Netherlands.
Prins
A
A
Visser
T
T
Wognum
B
B
Wagemaker
G
G
Löwenberg
B
B
Wielenga
J
J
D000208:Acute Disease; D000818:Animals; D005260:Female; D006085:Graft Survival; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000473:pathology*; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000379:methods; D013047:Specific Pathogen-Free Organisms; D014916:Whole-Body Irradiation
D007377:Interleukin-3