Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML.

作者: AB Deisseroth , Z Zu , D Claxton , EG Hanania , S Fu

DOI: 10.1182/BLOOD.V83.10.3068.3068

关键词:

摘要: Relapse after autologous bone marrow transplantation for chronic myelogenous leukemia (CML) can be due either to the persistence of cells in systemic tissues following preparative therapy, or used restore function intensive therapy. To help distinguish between these two possible causes relapse, we safety-modified retroviruses, which contain bacterial resistance gene NEO, mark that had been collected from patients early phase hematopoietic recovery vivo chemotherapy. The were then subjected ex CD34 selection collection and 30% exposed a virus. This was infused delivery consisted total body irradiation (1,020 cGy), cyclophosphamide (120 mg/kg), VP-16 (750 mg/m2). RT PCR assays specific NEO mRNA, coded by virus, bcr-abl mRNA showed evaluable CML transplanted with marked cells, sufficient numbers remained contribute relapse. In addition, both normal leukemic positive retroviral transgenome persisted circulation at least 280 days posttransplant showing responsible return hematopoiesis observation shows it is use replication-incompetent retrovirus order introduce DNA sequences into undergoing transplantation. Moreover, this data suggested additional fractionation procedures will necessary reduce probability relapse advanced stages disease procedures.

参考文章(9)
David Claxton, Soon-Pal Suh, Marylynńe Filaccio, Debra Ellerson, Eugenia Gaozza, Borje Andersson, Malcolm Brenner, Christopher Reading, Andrew Feinberg, Robert Moen, John Belmont, Kateri Moore, Moshe Talpaz, Hagop Kantarjian, Albert Deisseroth, Molecular analysis of retroviral transduction in chronic myelogenous leukemia. Human Gene Therapy. ,vol. 2, pp. 317- 321 ,(1991) , 10.1089/HUM.1991.2.4-317
A. M. Carella, N. Pollicardo, E. Pungolino, M. R. Raffo, M. Podesta, R. Ferrero, D. Pierluigi, S. Nati, K. Naibo, A. Congiu, M. Spriano, R. Vimercati, O. Figari, C. Rosso, G. Saglio, M. Sessarego, G. Lercari, M. Valbonesi, P. Carlier, V. Vitale, P. Corvo, M. Parodi, Mobilization of Cytogenetically ‘Normal’ Blood Progenitors Cells by Intensive Conventional Chemotherapy for Chronic Myeloid and Acute Lymphoblastic Leukemia Leukemia & Lymphoma. ,vol. 9, pp. 477- 483 ,(1993) , 10.3109/10428199309145754
M.K. Brenner, V.M. Santana, D.R. Rill, M.S. Holladay, H.E. Heslop, M. Buschle, R.A. Krance, R.C. Moen, W.F. Anderson, J.N. Ihle, Gene marking to determine whether autologous marrow infusion restores long-term haemopoiesis in cancer patients The Lancet. ,vol. 342, pp. 1134- 1137 ,(1993) , 10.1016/0140-6736(93)92122-A
D. R. Rill, M. Buschle, N. K. Foreman, C. Bartholomew, R. C. Moen, V. M. Santana, J. N. Ihle, M. K. Brenner, Retrovirus-mediated gene transfer as an approach to analyze neuroblastoma relapse after autologous bone marrow transplantation. Human Gene Therapy. ,vol. 3, pp. 129- 136 ,(1992) , 10.1089/HUM.1992.3.2-129
Marc Etkin, Marylynne Filaccio, Debra Ellerson, Soon-Pal Suh, David Claxton, Eugenia Gaozza, Malcolm Brenner, Robert Moen, John Belmont, Kateri A. Moore, A. M. Moseley, Christopher Reading, Issa Khouri, Moshe Talpaz, Hagop Kantarjian, Albert Deisseroth, Use of Cell-Free Retroviral Vector Preparations for Transduction of Cells from the Marrow of Chronic Phase and Blast Crisis Chronic Myelogenous Leukemia Patients and from Normal Individuals Human Gene Therapy. ,vol. 3, pp. 137- 145 ,(1992) , 10.1089/HUM.1992.3.2-137
Hagop M. Kantarjian, Charles F. Lemaistre, Jorge Spinolo, Gary Spitzer, Jonathan Yau, Karel Dicke, Sundar Jagannath, Albert B. Deisseroth, Moshe Talpaz, Intensive combination chemotherapy and autologous bone marrow transplantation leads to the reappearance of Philadelphia chromosome-negative cells in chronic myelogenous leukemia. Cancer. ,vol. 67, pp. 2959- 2965 ,(1991) , 10.1002/1097-0142(19910615)67:12<2959::AID-CNCR2820671203>3.0.CO;2-T
DR Rill, RC Moen, M Buschle, C Bartholomew, NK Foreman, J Jr Mirro, RA Krance, JN Ihle, MK Brenner, An approach for the analysis of relapse and marrow reconstitution after autologous marrow transplantation using retrovirus-mediated gene transfer. Blood. ,vol. 79, pp. 2694- 2700 ,(1992) , 10.1182/BLOOD.V79.10.2694.2694