No Evidence of Clonal Dominance after Transplant of HOXB4-Expanded Cord Blood Cells in a Nonhuman Primate Model.

Publication Type:

Journal Article


Experimental hematology (2014)


2014, April 2014, Clinical Research Division


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 prior to transplant, including overexpression of the HOXB4 transcription factor. We have previously reported the development of leukemia in several nonhuman primate subjects transplanted with HOXB4-expanded bone marrow cells at approximately 2 years post-transplant. Here, we provide long-term data for a nonhuman primate receiving a HOXB4-expanded cord blood graft. Longitudinal follow-up included gene marking analysis, complete blood counts, morphological/pathological 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-modiifed bone marrow cells showed that dominant clones could be detected as early as 6 months post-transplant 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.