Transplantation of syngenic bone marrow contaminated with NGFr-marked WEHI-3B cells: an improved model of leukemia relapse in mice.
With the aim of developing a model mimicking the relapse of patients transplanted with leukemia-contaminated grafts, myelomonocytic leukemia WEHI-3B D+ cells were first transduced with a retroviral vector encoding the low-affinity human nerve growth factor receptor (NGFr). Clones with a stable and homogeneous expression of the transgene and with a similar in vitro behavior to the parental cell line were selected for further experiments. The analysis of bone marrow (BM) contaminated with WEHI-3B/NGFr cells revealed a linear correlation (r2 = 0.999) between the actual values of BM contamination and the experimental data determined by flow cytometry. Balb/c mice were myeloablated and transplanted with syngenic BM contaminated with graded numbers of leukemic cells; dose-dependent survival curves were obtained, regardless of whether parental or WEHI-3B/NGFr cells were infused. The leukemia dissemination in recipients transplanted with WEHI-3B/NGFr contaminated grafts was easily determined by means of simple flow cytometry analysis of the NGFr marker. A leukemia dose-dependent increase in the number of PB leukocytes was observed in transplanted recipients at 20 days post-transplantation with no changes in myelomonocytic cells. As deduced from our observations, the transplantation of syngenic BM contaminated with WEHI-3B/NGFr cells constitutes an improved model of autograft-mediated leukemia relapse and a good tool for studies of leukemia cell purging.
García-Castro
J
J
Unidad de Biología Molecular y Celular, CIEMAT, Madrid, Spain.
Segovia
J C
JC
Bueren
J A
JA
D000818:Animals; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002452:Cell Count; D004273:DNA, Neoplasm / Q000032:analysis; D004195:Disease Models, Animal; D005434:Flow Cytometry; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D009368:Neoplasm Transplantation; D011828:Radiation Chimera; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D014182:Transplantation, Autologous / Q000009:adverse effects*; D017211:Treatment Failure; D014407:Tumor Cells, Cultured / Q000637:transplantation* / Q000821:virology
D004273:DNA, Neoplasm; D017475:Receptors, Nerve Growth Factor