Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy

E. G. Hanania, R. E. Giles, J. Kavanagh, D. Ellerson, Z. Zu, T. Wang, Y. Su, A. Kudelka, Z. Rahman, F. Holmes, G. Hortobagyi, D. Claxton, C. Bachier, P. Thall, S. Cheng, J. Hester, J. M. Ostrove, R. E. Bird, A. Chang, M. KorblingD. Seong, R. Cote, T. Holzmayer, E. Mechetner, S. Heimfeld, R. Berenson, B. Burtness, C. Edwards, R. Bast, M. Andreeff, R. Champlin, A. B. Deisseroth

Research output: Contribution to journalArticle

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Abstract

To formally test the hypothesis that the granulocyte/macrophage colony-forming unit (GM-CFU) cells can contribute to early hematopoietic reconstitution immediately after transplant, the frequency of genetically modified GM-CFU after retroviral vector transduction was measured by a quantitative in situ polymerase chain reaction (PCR), which is specific for the multidrug resistance-1 (MDR-1) vector, and by a quantitative GM-CFU methylcellulose plating assay. The results of this analysis showed no difference between the transduction frequency in the products of two different transduction protocols: "suspension transduction" and "stromal growth factor transduction." However, when an analysis of the frequency of cells positive for the retroviral MDR-1 vector posttransplantation was carried out, 0 of 10 patients transplanted with cells transduced by the suspension method were positive for the vector MDR-1 posttransplant, whereas 5 of 8 patients transplanted with the cells transduced by the stromal growth factor method were positive for the MDR-1 vector transcription unit by in situ or in solution PCR assay (a difference that is significant at the P = 0.0065 level by the Fisher exact test). These data suggest that only very small subsets of the GM-CFU fraction of myeloid cells, if any, contribute to the repopulation of the hematopoietic tissues that occurs following intensive systemic therapy and transplantation of autologous hematopoietic cells.

Original languageEnglish
Pages (from-to)15346-15351
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number26
DOIs
StatePublished - Dec 24 1996
Externally publishedYes

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    Hanania, E. G., Giles, R. E., Kavanagh, J., Ellerson, D., Zu, Z., Wang, T., Su, Y., Kudelka, A., Rahman, Z., Holmes, F., Hortobagyi, G., Claxton, D., Bachier, C., Thall, P., Cheng, S., Hester, J., Ostrove, J. M., Bird, R. E., Chang, A., ... Deisseroth, A. B. (1996). Results of MDR-1 vector modification trial indicate that granulocyte/macrophage colony-forming unit cells do not contribute to posttransplant hematopoietic recovery following intensive systemic therapy. Proceedings of the National Academy of Sciences of the United States of America, 93(26), 15346-15351. https://doi.org/10.1073/pnas.93.26.15346