Transmission and expansion of HOXB4-induced leukemia in two immunosuppressed dogs: implications for a new canine leukemia model. Exp Hematol 2009 Oct;37(10):1157-66
Date
07/21/2009Pubmed ID
19616601Pubmed Central ID
PMC2748853DOI
10.1016/j.exphem.2009.07.004Scopus ID
2-s2.0-70249133659 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
OBJECTIVE: There are currently no large animal models to study the biology of leukemia and development of novel antileukemia therapies. We have previously shown that dogs transplanted with homeobox B4 (HOXB4)-transduced autologous CD34(+) cells developed myeloid leukemia associated with HOXB4 overexpression. Here we describe the transmission, engraftment, and expansion of these canine leukemia cells into two genetically unrelated, immunosuppressed dogs.
MATERIALS AND METHODS: Two dogs immunosuppressed after major histocompatibility complex-haploidentical hematopoietic cell transplantation and exhibiting mixed donor-host chimerism were accidentally infused trace amounts of HOXB4-overexpressing leukemia cells from a third-party dog.
RESULTS: Six weeks after infusion of HOXB4-overexpressing leukemia cells, these two dogs rapidly developed myeloid leukemia consisting of marrow and organ infiltration, circulating blasts, and, in one dog, chloromatous masses. Despite neither of these dogs sharing any dog leukocyte antigen haplotypes with the sentinel case, the HOXB4-transduced clones engrafted and proliferated without difficulty in the presence of immunosuppression. Chimerism studies in both dogs confirmed that donor and, in one case, host hematopoietic cell engraftment was lost and replaced by third-party HOXB4 cells.
CONCLUSIONS: The engraftment and expansion of these leukemia cells in dogs will allow studies into the biology of leukemia and development and evaluation of novel antileukemia therapies in a clinically relevant large animal model.
Author List
Thakar MS, Zhang XB, Beard BC, Sale GE, Santos EB, Peterson L, Kiem HP, Sandmaier BMMESH terms used to index this publication - Major topics in bold
AccidentsAnimals
Catheterization
Cell Line, Tumor
Disease Models, Animal
Dogs
Equipment Contamination
Fluid Therapy
Genes, Reporter
Genetic Vectors
Green Fluorescent Proteins
Hematopoietic Stem Cell Transplantation
Histocompatibility Antigens Class I
Homeodomain Proteins
Immunocompromised Host
Immunosuppressive Agents
Leukemia, Myeloid
Minisatellite Repeats
Neoplasm Transplantation
Neoplastic Stem Cells
Radiation Chimera
Recombinant Fusion Proteins
Transcription Factors
