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Science 2 December 1988:
Vol. 242. no. 4883, pp. 1303 - 1306
DOI: 10.1126/science.2461588
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Articles

Science, Vol 242, Issue 4883, 1303-1306
Copyright © 1988 by American Association for the Advancement of Science

articles

A c-myb antisense oligodeoxynucleotide inhibits normal human hematopoiesis in vitro

AM Gewirtz and B Calabretta

Department of Medicine, University School of Medicine, Philadelphia, PA 19140.

The nuclear protein encoded by the proto-oncogene c-myb has been hypothesized to play an important role in the process of hematopoiesis, but direct proof of this function has been lacking. To address this issue, normal human bone marrow mononuclear cells were exposed to c-myb sense and antisense synthetic oligodeoxynucleotides, and the effects on hematopoietic colony formation and maturation were examined. Exposure of these cells to c-myb antisense, oligodeoxynucleotides resulted in a decrease in both colony size and number, without apparent effect on the maturation of residual colony cells. Exposure to c-myb sense, or irrelevant antisense, oligonucleotides had no such effect. These results show that (i) c-myb plays a critical role in regulating normal human hematopoiesis and (ii) the combined use of antisense oligodeoxynucleotides and hematopoietic cell culture techniques will provide a powerful tool for studying the role of proteins encoded by proto-oncogenes, or other specific genes, in normal human hematopoiesis.


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Granulocytic Differentiation of Normal Hematopoietic Precursor Cells Induced by Transcription Factor PU.1 Correlates With Negative Regulation of the c-myb Promoter.
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Murine A-myb Gene Encodes a Transcription Factor, Which Cooperates with Ets-2 and Exhibits Distinctive Biochemical and Biological Activities from c-myb.
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Transcription Factors, Normal Myeloid Development, and Leukemia.
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c-Myb–Dependent Cell Cycle Progression and Ca2+ Storage in Cultured Vascular Smooth Muscle Cells.
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c-Myb trans-Activates the Human DNA Topoisomerase IIalpha Gene Promoter.
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Identification of the Major Positive Regulators of c-myb Expression in Hematopoietic Cells of Different Lineages.
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Differential Regulation of c-Myb-induced Transcription Activation by a Phosphorylation Site in the Negative Regulatory Domain.
M. R. Miglarese, A. F. Richardson, N. Aziz, and T. P. Bender (1996)
J. Biol. Chem. 271, 22697-22705
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CBP as a transcriptional coactivator of c-Myb..
P Dai, H Akimaru, Y Tanaka, D X Hou, T Yasukawa, C Kanei-Ishii, T Takahashi, and S Ishii (1996)
Genes & Dev. 10, 528-540
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Repression of the c-myb Gene by WT1 Protein in T and B Cell Lines.
S. McCann, J. Sullivan, J. Guerra, M. Arcinas, and L. M. Boxer (1995)
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c-Myb Repression of c- erbB-2 Transcription by Direct Binding to the c- erbB-2 Promoter.
G. Mizuguchi, C. Kanei-Ishii, T. Takahashi, T. Yasukawa, T. Nagase, M. Horikoshi, T. Yamamoto, and S. Ishii (1995)
J. Biol. Chem. 270, 9384-9389
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Requirement of B- myb Function for Survival and Differentiative Potential of Human Neuroblastoma Cells.
G. Raschell, A. Negroni, A. Sala, S. Pucci, A. Romeo, and B. Calabretta (1995)
J. Biol. Chem. 270, 8540-8545
   Abstract »    Full Text »    PDF »
Members of the Nuclear Factor kappaB Family Transactivate the Murine c-myb Gene.
C. R. Toth, R. F. Hostutler, A. S.:Jr. Baldwin, and T. P. Bender (1995)
J. Biol. Chem. 270, 7661-7671
   Abstract »    Full Text »    PDF »
Structural and Functional Studies of the Intracellular Tyrosine Kinase MATK Gene and Its Translated Product.
S. Avraham, S. Jiang, S. Ota, Y. Fu, B. Deng, L. L. Dowler, R. A. White, and H. Avraham (1995)
J. Biol. Chem. 270, 1833-1842
   Abstract »    Full Text »    PDF »
An antisense oligodeoxyribonucleotide to m-calpain mRNA inhibits myoblast fusion.
D Balcerzak, S Poussard, J. Brustis, N Elamrani, M Soriano, P Cottin, and A Ducastaing (1995)
J. Cell Sci. 108, 2077-2082
   Abstract »    PDF »
Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells..
M J Weiss, G Keller, and S H Orkin (1994)
Genes & Dev. 8, 1184-1197
   Abstract »    PDF »
Dominant interfering alleles define a role for c-Myb in T-cell development..
P Badiani, P Corbella, D Kioussis, J Marvel, and K Weston (1994)
Genes & Dev. 8, 770-782
   Abstract »    PDF »
Myb and NF-M: combinatorial activators of myeloid genes in heterologous cell types..
S A Ness, E Kowenz-Leutz, T Casini, T Graf, and A Leutz (1993)
Genes & Dev. 7, 749-759
   Abstract »    PDF »
Carboxy-terminal elements of c-Myb negatively regulate transcriptional activation in cis and in trans..
J W Dubendorff, L J Whittaker, J T Eltman, and J S Lipsick (1992)
Genes & Dev. 6, 2524-2535
   Abstract »    PDF »
Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides.
C Szczylik, T Skorski, N. Nicolaides, L Manzella, L Malaguarnera, D Venturelli, A. Gewirtz, and B Calabretta (1991)
Science 253, 562-565
   Abstract »    PDF »
New light on Myc and Myb. Part II. Myb..
B Luscher and R N Eisenman (1990)
Genes & Dev. 4, 2235-2241
   PDF »
Extension of the life-span of human endothelial cells by an interleukin-1 alpha antisense oligomer.
J. Maier, P Voulalas, D Roeder, and T Maciag (1990)
Science 249, 1570-1574
   Abstract »    PDF »
Differentiation of mouse erythroleukemia cells enhanced by alternatively spliced c-myb mRNA.
B. Weber, E. Westin, and M. Clarke (1990)
Science 249, 1291-1293
   Abstract »    PDF »
Activation of transcription by v-myb: evidence for two different mechanisms..
K H Klempnauer, H Arnold, and H Biedenkapp (1989)
Genes & Dev. 3, 1582-1589
   Abstract »    PDF »
Lineage-specific requirement of c-abl function in normal hematopoiesis.
D Caracciolo, M Valtieri, D Venturelli, C Peschle, A. Gewirtz, and B Calabretta (1989)
Science 245, 1107-1110
   Abstract »    PDF »
G1/S transition in normal human T-lymphocytes requires the nuclear protein encoded by c-myb.
A. Gewirtz, G Anfossi, D Venturelli, S Valpreda, R Sims, and B Calabretta (1989)
Science 245, 180-183
   Abstract »    PDF »


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