|
|
Next Article 
Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 731-737
PLENARY PAPER
In vivo inhibition by a site-specific catalytic RNA subunit of
RNase P designed against the BCR-ABL oncogenic products: a novel
approach for cancer treatment
C. Cobaleda and
I. Sánchez-García
From the Department of Cell Growth and Differentiation, Institute of
Microbiology and Biochemistry, CSIC/University of Salamanca, Salamanca,
Spain.
One major obstacle to the effective treatment of cancer is to
distinguish between tumor cells and normal cells. The chimeric molecules created by cancer-associated chromosomal abnormalities are
ideal therapeutic targets because they are unique to the disease. We describe the use of a novel approach based on the catalytic RNA subunit of RNase P to destroy specifically the tumor-specific fusion genes created as a result of chromosome abnormalities. Using as
a target model the abnormal BCR-ABL p190 and p210 products, we
constructed M1-RNA with guide sequences that recognized the oncogenic
messengers at the fusion point (M1-p190-GS and M1-p210-GS). To test the
effectiveness and the specificity of M1-p190-GS and M1-p210-GS, we
studied in vitro and in vivo effects of these RNA enzymes against
BCR-ABLp190 and
BCR-ABLp210, bearing in mind that both
fusion genes share the ABL sequence but differ in the sequence
coming from the BCR gene. We showed that
M1-p190-GS and M1-p210-GS can act as sequence-specific endonucleases and can exclusively cleave target RNA that forms a base pair with the
guide sequence (GS). We also demonstrated that when M1-p190-GS and
M1-p210-GS were expressed in proper mammalian cell models, they
abolished the effect of BCR-ABL by specifically decreasing the
amount of the target BCR-ABL mRNA and preventing the function of the
BCR-ABL oncogenes. These data clearly demonstrate the
usefulness of the catalytic activity of M1-GS RNA to cleave
specifically the chimeric molecules created by chromosomal
abnormalities in human cancer and to represent a novel approach to
cancer treatment.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. H. Mak, W. D. Schober, W. Chen, M. Konopleva, J. Cortes, H. M. Kantarjian, M. Andreeff, and B. Z. Carter
Triptolide induces cell death independent of cellular responses to imatinib in blast crisis chronic myelogenous leukemia cells including quiescent CD34+ primitive progenitor cells
Mol. Cancer Ther.,
September 1, 2009;
8(9):
2509 - 2516.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Bai, P. Trang, H. Li, K. Kim, T. Zhou, and F. Liu
Effective inhibition in animals of viral pathogenesis by a ribozyme derived from RNase P catalytic RNA
PNAS,
August 5, 2008;
105(31):
10919 - 10924.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. A. Bartholomeusz, M. Talpaz, V. Kapuria, L. Y. Kong, S. Wang, Z. Estrov, W. Priebe, J. Wu, and N. J. Donato
Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells
Blood,
April 15, 2007;
109(8):
3470 - 3478.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. C. Deocaris, S. C. Kaul, K. Taira, and R. Wadhwa
Emerging Technologies: Trendy RNA Tools for Aging Research
J. Gerontol. A Biol. Sci. Med. Sci.,
August 1, 2004;
59(8):
B771 - B783.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. KIM, S. UMAMOTO, P. TRANG, R. HAI, and F. LIU
Intracellular expression of engineered RNase P ribozymes effectively blocks gene expression and replication of human cytomegalovirus
RNA,
March 1, 2004;
10(3):
438 - 447.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Nimmanapalli, P. Bali, E. O'Bryan, L. Fuino, F. Guo, J. Wu, P. Houghton, and K. Bhalla
Arsenic Trioxide Inhibits Translation of mRNA of bcr-abl, Resulting in Attenuation of Bcr-Abl Levels and Apoptosis of Human Leukemia Cells
Cancer Res.,
November 15, 2003;
63(22):
7950 - 7958.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Zou, J. Lee, S. Umamoto, A. F. Kilani, J. Kim, P. Trang, T. Zhou, and F. Liu
Engineered RNase P Ribozymes Are Efficient in Cleaving a Human Cytomegalovirus mRNA in Vitro and Are Effective in Inhibiting Viral Gene Expression and Growth in Human Cells
J. Biol. Chem.,
September 26, 2003;
278(39):
37265 - 37274.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. V. Melo, T. P. Hughes, and J. F. Apperley
Chronic Myeloid Leukemia
Hematology,
January 1, 2003;
2003(1):
132 - 152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Nimmanapalli, E. O'Bryan, M. Huang, P. Bali, P. K. Burnette, T. Loughran, J. Tepperberg, R. Jove, and K. Bhalla
Molecular Characterization and Sensitivity of STI-571 (Imatinib Mesylate, Gleevec)-resistant, Bcr-Abl-positive, Human Acute Leukemia Cells to SRC Kinase Inhibitor PD180970 and 17-Allylamino-17-demethoxygeldanamycin
Cancer Res.,
October 15, 2002;
62(20):
5761 - 5769.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Kraus, R. Geffin, G. Spruill, A. K. Young, R. Seivright, D. Cardona, J. Burzawa, and H. J. Hnatyszyn
Cross-clade inhibition of HIV-1 replication and cytopathology by using RNase P-associated external guide sequences
PNAS,
March 19, 2002;
99(6):
3406 - 3411.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Gopalan, A. Vioque, and S. Altman
RNase P: Variations and Uses
J. Biol. Chem.,
February 22, 2002;
277(9):
6759 - 6762.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Trang, J. Lee, A. F. Kilani, J. Kim, and F. Liu
Effective inhibition of herpes simplex virus 1 gene expression and growth by engineered RNase P ribozyme
Nucleic Acids Res.,
December 15, 2001;
29(24):
5071 - 5078.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Nimmanapalli, E. O’Bryan, and K. Bhalla
Geldanamycin and Its Analogue 17-Allylamino-17-demethoxygeldanamycin Lowers Bcr-Abl Levels and Induces Apoptosis and Differentiation of Bcr-Abl-positive Human Leukemic Blasts
Cancer Res.,
March 1, 2001;
61(5):
1799 - 1804.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
E. Laurent, M. Talpaz, H. Kantarjian, and R. Kurzrock
The BCR Gene and Philadelphia Chromosome-positive Leukemogenesis
Cancer Res.,
March 1, 2001;
61(6):
2343 - 2355.
[Full Text]
|
|
|
|
|
|
|
R. Nimmanapalli, M. Porosnicu, D. Nguyen, E. Worthington, E. O’Bryan, C. Perkins, and K. Bhalla
Cotreatment with STI-571 Enhances Tumor Necrosis Factor {{alpha}}-related Apoptosis-inducing Ligand (TRAIL or Apo-2L)- induced Apoptosis of Bcr-Abl-positive Human Acute Leukemia Cells
Clin. Cancer Res.,
February 1, 2001;
7(2):
350 - 357.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. W. N. Deininger, J. M. Goldman, and J. V. Melo
The molecular biology of chronic myeloid leukemia
Blood,
November 15, 2000;
96(10):
3343 - 3356.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-M. Lim, S. Wong, G. Lau, O. N. Witte, and J. Colicelli
BCR/ABL inhibition by an escort/phosphatase fusion protein
PNAS,
October 4, 2000;
(2000)
210253497.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
H. Kantarjian, J. V. Melo, S. Tura, S. Giralt, and M. Talpaz
Chronic Myelogenous Leukemia: Disease Biology and Current and Future Therapeutic Strategies
Hematology,
January 1, 2000;
2000(1):
90 - 109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-M. Lim, S. Wong, G. Lau, O. N. Witte, and J. Colicelli
BCR/ABL inhibition by an escort/phosphatase fusion protein
PNAS,
October 24, 2000;
97(22):
12233 - 12238.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
