No evidence of clonal dominance after transplant of HOXB4-expanded cord blood cells in a nonhuman primate model.
Umbilical cord blood transplant continues to increase in prevalence as a treatment option for various hematopoietic and immune disorders. Because of the limited number of cells available in a single cord blood unit, investigators have explored methods of increasing cell dose before transplant, including overexpression of the homeobox B4 (HOXB4) transcription factor. We have previously reported the development of leukemia in several nonhuman primate (NHP) subjects transplanted with HOXB4-expanded bone marrow cells at approximately 2 years posttransplant. Here, we provide long-term data for a NHP receiving a HOXB4-expanded cord blood graft. Longitudinal follow-up included gene marking analysis, complete blood counts, morphologic/pathologic assessment, phenotypic analysis of subsets, and retroviral integration site analysis. In each of these independent assays, we saw no indication of clonal dominance, and all signs pointed toward normal, healthy hematopoiesis. Furthermore, in-depth clonal analysis of an animal that developed leukemia after transplantation of HOXB4-modified bone marrow cells showed that dominant clones could be detected as early as 6 months posttransplant using the genomic analysis technique detailed here. Parallel analysis of the cord blood transplant macaque showed no such sites. These findings demonstrate the ability to study the use of gene-modified and expanded cord blood cells in a NHP model.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Korashon L
KL
Watts
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA.
Brian C
BC
Beard
Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
Brent L
BL
Wood
Department of Pharmaceutical Sciences, Washington State University, Pullman, WA, USA.
Grant D
GD
Trobridge
Terry Fox Laboratory, British Columbia Cancer Agency and Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
R Keith
RK
Humphries
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Amie B
AB
Adams
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Veronica
V
Nelson
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: hkiem@fhcrc.org.
Hans-Peter
HP
Kiem
D000818:Animals; D005819:Genetic Markers; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008254:Macaca nemestrina; D023421:Models, Animal; D011323:Primates; D033581:Stem Cell Transplantation; D014157:Transcription Factors / Q000235:genetics*
D005819:Genetic Markers; C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors