Specific Killing of Ph+ Chronic Myeloid Leukemia Cells by a Lentiviral Vector-Delivered Anti-bcr/abl Small Hairpin RNA

Ming Jie Li, Ross McMahon, David S. Snyder, Jiing Kuan Yee, John J. Rossi

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Chronic myeloid leukemia (CML) is characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 t(9;22)(q34;q11) that causes fusion of the bcr and abl genes. Transcription and splicing of the fusion gene generate two major splice variants of the bcr/abl transcript that encode an oncoprotein with tyrosine kinase activity. We have taken advantage of lentiviral vector-mediated delivery of anti-bcr/abl short hairpin RNAs (shRNA) to downregulate the bcr/abl transcript in Philadelphia chromosome-positive (Ph+) K562 leukemia cells. This downregulation caused complete inhibition of proliferation of these cells and was accompanied by >90% inhibition of the bcr/abl transcript and p210 protein. These results demonstrate the feasibility of using a lentiviral vector to stably transduce therapeutic shRNAs into leukemia cells for the potential ex vivo purging of Ph+ cells in an autologous hematopoietic cell transplant setting. Furthermore, the robust expression of the shRNAs from our lentiviral vector suggests that this system could be generally useful for the expression of other shRNAs.

Original languageEnglish
Pages (from-to)401-409
Number of pages9
JournalOligonucleotides
Volume13
Issue number5
DOIs
StatePublished - Dec 1 2003

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