|
|
 Previous Article | Table of Contents | Next Article 
Clonal evolution in a myeloid cell line transformed to interleukin-3
independent growth by retroviral transduction and expression of p210bcr/abl
P Laneuville, G Sun, M Timm and M Vekemans
Department of Medicine, Royal Victoria Hospital, Montreal, Quebec, Canada.
Current evidence suggests that the expression of the tyrosine kinase
p210bcr/abl in chronic myelogenous leukemia (CML) may directly induce the
initial phase of granulocytic hyperplasia. However, the dysregulation of
additional genes appears to be required for transition to the acute
leukemic phase, as inferred by the appearance of recurrent secondary
cytogenetic abnormalities in the majority of patients. To determine whether
the expression of p210bcr/abl alone is responsible for this genetic
instability, we introduced and expressed the bcr/abl gene from a retroviral
vector in a clone of the interleukin-3 (IL-3) dependent myeloblastic 32D
C13(G) cell line. Clonal and polyclonal cells transformed to IL-3
independent growth were observed for a period extending up to 6 months for
changes in the expression of p210bcr/abl, cell proliferation, inhibition by
prostaglandin E1 (PGE1), forskolin, and cyclic adenosine monophosphate
(cAMP) analogues, regulation of the cell cycle, and karyotype. Whereas the
properties of control vector infected 32D C13(G)' cells remained stable
over time, cells expressing p210bcr/abl were phenotypically unstable. In
cells expressing p210bcr/abl, we observed selective modulation of
p210bcr/abl mRNA and protein expression, evolution from partial to full
abrogation of IL-3 dependence, reduced serum requirements, increased cell
proliferation, decreased inhibition by PGE1 and cAMP analogues, and the
appearance of new structural and numerical chromosomal abnormalities with
successive cell passages. These results indicate that expression of
p210bcr/abl can directly predispose 32D C13(G)' cells to genetic
instability, promotes the emergence of clones with an increased
proliferative advantage, and may represent an in vitro model suitable for
the study of mechanisms underlying progression to the acute leukemic phase
in CML.
Volume 80,
Issue 7,
pp. 1788-1797,
10/01/1992
Copyright © 1992 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. McCallum, S. Price, N. Planque, B. Perbal, A. Pierce, A. D. Whetton, and A. E. Irvine
A novel mechanism for BCR-ABL action: stimulated secretion of CCN3 is involved in growth and differentiation regulation
Blood,
September 1, 2006;
108(5):
1716 - 1723.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Koptyra, R. Falinski, M. O. Nowicki, T. Stoklosa, I. Majsterek, M. Nieborowska-Skorska, J. Blasiak, and T. Skorski
BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance
Blood,
July 1, 2006;
108(1):
319 - 327.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Calabretta and D. Perrotti
The biology of CML blast crisis
Blood,
June 1, 2004;
103(11):
4010 - 4022.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Brain, N. Goodyer, and P. Laneuville
Measurement of Genomic Instability in Preleukemic P190BCR/ABL Transgenic Mice Using Inter-Simple Sequence Repeat Polymerase Chain Reaction
Cancer Res.,
August 15, 2003;
63(16):
4895 - 4898.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Salesse and C. M. Verfaillie
BCR/ABL-mediated Increased Expression of Multiple Known and Novel Genes That May Contribute to the Pathogenesis of Chronic Myelogenous Leukemia
Mol. Cancer Ther.,
February 1, 2003;
2(2):
173 - 182.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. G. Savage and K. H. Antman
Imatinib Mesylate -- A New Oral Targeted Therapy
N. Engl. J. Med.,
February 28, 2002;
346(9):
683 - 693.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. W. Goetz, H. van der Kuip, R. Maya, M. Oren, and W. E. Aulitzky
Requirement for Mdm2 in the Survival Effects of Bcr-Abl and Interleukin 3 in Hematopoietic Cells
Cancer Res.,
October 1, 2001;
61(20):
7635 - 7641.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Deutsch, A. Dugray, B. AbdulKarim, E. Marangoni, L. Maggiorella, S. Vaganay, R. M'Kacher, S. D. Rasy, F. Eschwege, W. Vainchenker, et al.
BCR-ABL down-regulates the DNA repair protein DNA-PKcs
Blood,
April 1, 2001;
97(7):
2084 - 2090.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. Zimonjic, J. L. Pollock, P. Westervelt, N. C. Popescu, and T. J. Ley
Acquired, nonrandom chromosomal abnormalities associated with the development of acute promyelocytic leukemia in transgenic mice
PNAS,
November 21, 2000;
97(24):
13306 - 13311.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. T. Thiesing, S. Ohno-Jones, K. S. Kolibaba, and B. J. Druker
Efficacy of STI571, an Abl tyrosine kinase inhibitor, in conjunction with other antileukemic agents against Bcr-Abl-positive cells
Blood,
November 1, 2000;
96(9):
3195 - 3199.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Jonuleit, H. van der Kuip, C. Miething, H. Michels, M. Hallek, J. Duyster, and W. E. Aulitzky
Bcr-Abl kinase down-regulates cyclin-dependent kinase inhibitor p27 in human and murine cell lines
Blood,
September 1, 2000;
96(5):
1933 - 1939.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Agliano, C. Santangelo, I. Silvestri, P. Gazzaniga, L. Giuliani, G. Naso, L. Frati, and R. Castiglia
On chromosomal instability: what is the karyotype of your 32D Cl3 cell line?
Blood,
June 1, 2000;
95(11):
3636 - 3637.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Klucher, D. V. Lopez, and G. Q. Daley
Secondary Mutation Maintains the Transformed State in BaF3 Cells With Inducible BCR/ABL Expression
Blood,
May 15, 1998;
91(10):
3927 - 3934.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
