Total body irradiation and syngeneic marrow transplantation in an inbred rat model of acute myelogenous leukemia

• Published in: International journal of radiation oncology, biology, physics Vol. 4; no. 5; pp. 421 - 427
• Main Authors: Greenberger, Joel S., Lockwood, Charles J., France, Dennis S., McGrath, Thomas, Moloney, William C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.1978
• Subjects: Animals; Bone Marrow - drug effects; Bone Marrow - radiation effects; Bone Marrow Transplantation; Busulfan - pharmacology; Cyclophosphamide - pharmacology; Disease Models, Animal; Leukemia, Experimental - blood; Leukemia, Experimental - therapy; Leukemia, Myeloid, Acute - blood; Leukemia, Myeloid, Acute - therapy; Leukocyte Count; Rat acute myelogenous leukemia; Rats; Rats, Inbred WF; Recurrence; Total body irradiation; Transplantation, Isogeneic; Bone marrow transplantation; Rat acute myelogenous leukemia; Total body irradiation
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/0360-3016(78)90072-X

While acute myelogenous leukemia (AML) occurs rarely in laboratory animals, over 20 model systems have been reported. One of these, AML of the inbred Wistar/Furth Rat, has been shown to be pathophysiologically similar to human AML. Ten days after intravenous inoculation of 1.0 × 10 6 cells of a tissue culture grown clonal line, rats demonstrated peripheral blood leukemia, replacement of greater than 90% of the bone marrow with distinctive malignant myeloblasts and a syndrome of hypermuramidase (lysozyme) emia and muramidasuria. Total body irradiation (TBI) at 10 days after leukemia cell passage with a marrow lethal dose (950 rad, 140 rad/min, 137Cs source, 663 kV) followed by intravenous inoculation of 5.0 × 10 8/kg viable syngeneic bone marrow cells produced transient complete remissions. Repopulation with transplanted marrow was detected along with increasing numbers of recognizable W Fu AML cells in peripheral blood, marrow and central nervous system. The delayed leukemia relapse in irradiated transplanted rats compared to irradiated non-transplanted controls suggests an interaction between surviving W Fu AML cells and transplanted marrow. This model may be of value in studies designing a therapeutic interaction against AML by donor marrow in the chemotherapy, immunotherapy, and total body irradiated patient.