|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3829-3840
Bcr-Abl Efficiently Induces a Myeloproliferative Disease and
Production of Excess Interleukin-3 and Granulocyte-Macrophage
Colony-Stimulating Factor in Mice: A Novel Model for Chronic
Myelogenous Leukemia
Xiaowu Zhang and
Ruibao Ren
From the Rosenstiel Basic Medical Sciences Research Center, the
Department of Biochemistry, and the Department of Biology, Brandeis
University, Waltham, MA.
The bcr-abl oncogene plays a critical role in causing
chronic myelogenous leukemia (CML). Effective laboratory animal models of CML are needed to study the molecular mechanisms by which the bcr-abl oncogene acts in the disease progression of CML. We
used a murine stem cell retroviral vector (MSCV) to transduce the
bcr-abl/p210 oncogene into mouse bone marrow cells and found
that expression of Bcr-Abl/p210 induced a myeloproliferative disorder
that resembled the chronic phase of human CML in 100% of bone marrow
transplanted mice in about 3 weeks. This CML-like disease was readily
transplanted to secondary recipient mice. Multiple clones of infected
cells were expanded in the primary recipients, but the leukemia was primarily monoclonal in the secondary recipient mice. Mutation analysis
demonstrated that the protein tyrosine kinase activity of Bcr-Abl/p210
was essential for its leukemogenic potential in vivo. Interestingly, we
found that the leukemic cells expressed excess interleukin-3 (IL-3) and
granulocyte-macrophage colony-stimulating factor (GM-CSF) in the
diseased mice. These studies demonstrate that expression of Bcr-Abl can
induce a CML-like leukemia in mice much more efficiently and
reproducibly than in previously reported mouse CML models, probably due
to efficient expression in the correct target cell(s). Our first use of
this model for analysis of the molecular mechanisms involved in CML
raises the possibility that excess expression of hematopoietic growth
factors such as IL-3 and GM-CSF may contribute to the clinical
phenotype of CML.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Agarwal, T. G. P. Bumm, A. S. Corbin, T. O'Hare, M. Loriaux, J. VanDyke, S. G. Willis, J. Deininger, K. I. Nakayama, B. J. Druker, et al.
Absence of SKP2 expression attenuates BCR-ABL-induced myeloproliferative disease
Blood,
September 1, 2008;
112(5):
1960 - 1970.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Lu, L. J.-S. Huang, and H. F. Lodish
Dimerization by a Cytokine Receptor Is Necessary for Constitutive Activation of JAK2V617F
J. Biol. Chem.,
February 29, 2008;
283(9):
5258 - 5266.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Parikh, R. Subrahmanyam, and R. Ren
Oncogenic NRAS, KRAS, and HRAS Exhibit Different Leukemogenic Potentials in Mice
Cancer Res.,
August 1, 2007;
67(15):
7139 - 7146.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Yan, J.-K. Luo, K. J. Ritchie, I. Sakai, K. Takeuchi, R. Ren, and D.-E. Zhang
Ubp43 regulates BCR-ABL leukemogenesis via the type 1 interferon receptor signaling
Blood,
July 1, 2007;
110(1):
305 - 312.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Modi, T. McDonald, S. Chu, J.-K. Yee, S. J. Forman, and R. Bhatia
Role of BCR/ABL gene-expression levels in determining the phenotype and imatinib sensitivity of transformed human hematopoietic cells
Blood,
June 15, 2007;
109(12):
5411 - 5421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Wang, D. Cai, C. Brendel, C. Barett, P. Erben, P. W. Manley, A. Hochhaus, A. Neubauer, and A. Burchert
Adaptive secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates imatinib and nilotinib resistance in BCR/ABL+ progenitors via JAK-2/STAT-5 pathway activation
Blood,
March 1, 2007;
109(5):
2147 - 2155.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Shackelford, C. Kenific, A. Blusztajn, S. Waxman, and R. Ren
Targeted Degradation of the AML1/MDS1/EVI1 Oncoprotein by Arsenic Trioxide
Cancer Res.,
December 1, 2006;
66(23):
11360 - 11369.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Parikh, R. Subrahmanyam, and R. Ren
Oncogenic NRAS rapidly and efficiently induces CMML- and AML-like diseases in mice
Blood,
October 1, 2006;
108(7):
2349 - 2357.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. J. Griswold, M. MacPartlin, T. Bumm, V. L. Goss, T. O'Hare, K. A. Lee, A. S. Corbin, E. P. Stoffregen, C. Smith, K. Johnson, et al.
Kinase domain mutants of bcr-abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinib.
Mol. Cell. Biol.,
August 1, 2006;
26(16):
6082 - 6093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Xu, Y. Yu, S. Zheng, X. Zhao, Q. Dong, Z. He, Y. Liang, Q. Lu, Y. Fang, X. Gan, et al.
Overexpression of Shp2 tyrosine phosphatase is implicated in leukemogenesis in adult human leukemia
Blood,
November 1, 2005;
106(9):
3142 - 3149.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Akimov, A. Ramezani, T. S. Hawley, and R. G. Hawley
Bypass of Senescence, Immortalization, and Transformation of Human Hematopoietic Progenitor Cells
Stem Cells,
September 1, 2005;
23(9):
1423 - 1433.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Deininger, E. Buchdunger, and B. J. Druker
The development of imatinib as a therapeutic agent for chronic myeloid leukemia
Blood,
April 1, 2005;
105(7):
2640 - 2653.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. W. Harder, C. Quilici, E. Naik, M. Inglese, N. Kountouri, A. Turner, K. Zlatic, D. M. Tarlinton, and M. L. Hibbs
Perturbed myelo/erythropoiesis in Lyn-deficient mice is similar to that in mice lacking the inhibitory phosphatases SHP-1 and SHIP-1
Blood,
December 15, 2004;
104(13):
3901 - 3910.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Wong, J. McLaughlin, D. Cheng, C. Zhang, K. M. Shokat, and O. N. Witte
Sole BCR-ABL inhibition is insufficient to eliminate all myeloproliferative disorder cell populations
PNAS,
December 14, 2004;
101(50):
17456 - 17461.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Ren
Restraining CML by adhesives
Blood,
October 1, 2004;
104(7):
1917 - 1918.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Guo, G. Z. Ferl, R. Deora, M. Riedinger, S. Yin, J. L. Kerwin, J. A. Loo, and O. N. Witte
A phosphorylation site in Bruton's tyrosine kinase selectively regulates B cell calcium signaling efficiency by altering phospholipase C-{gamma} activation
PNAS,
September 28, 2004;
101(39):
14180 - 14185.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Ramaraj, H. Singh, N. Niu, S. Chu, M. Holtz, J. K. Yee, and R. Bhatia
Effect of Mutational Inactivation of Tyrosine Kinase Activity on BCR/ABL-Induced Abnormalities in Cell Growth and Adhesion in Human Hematopoietic Progenitors
Cancer Res.,
August 1, 2004;
64(15):
5322 - 5331.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. P. Million, N. Harakawa, S. Roumiantsev, L. Varticovski, and R. A. Van Etten
A Direct Binding Site for Grb2 Contributes to Transformation and Leukemogenesis by the Tel-Abl (ETV6-Abl) Tyrosine Kinase
Mol. Cell. Biol.,
June 1, 2004;
24(11):
4685 - 4695.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. C. Matte, J. Cormier, B. E. Anderson, I. Athanasiadis, J. Liu, S. G. Emerson, W. Pear, and W. D. Shlomchik
Graft-versus-leukemia in a retrovirally induced murine CML model: mechanisms of T-cell killing
Blood,
June 1, 2004;
103(11):
4353 - 4361.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. Sykes and M. P. Kamps
E2a/Pbx1 Induces the Rapid Proliferation of Stem Cell Factor-Dependent Murine Pro-T Cells That Cause Acute T-Lymphoid or Myeloid Leukemias in Mice
Mol. Cell. Biol.,
February 1, 2004;
24(3):
1256 - 1269.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Guasch, B. Delaval, C. Arnoulet, M.-J. Xie, L. Xerri, D. Sainty, D. Birnbaum, and M.-J. Pebusque
FOP-FGFR1 tyrosine kinase, the product of a t(6;8) translocation, induces a fatal myeloproliferative disease in mice
Blood,
January 1, 2004;
103(1):
309 - 312.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Zhang, M. Socolovsky, A. W. Gross, and H. F. Lodish
Role of Ras signaling in erythroid differentiation of mouse fetal liver cells: functional analysis by a flow cytometry-based novel culture system
Blood,
December 1, 2003;
102(12):
3938 - 3946.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Goldman and J. V. Melo
Chronic Myeloid Leukemia -- Advances in Biology and New Approaches to Treatment
N. Engl. J. Med.,
October 9, 2003;
349(15):
1451 - 1464.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Wong, J. McLaughlin, D. Cheng, K. Shannon, L. Robb, and O. N. Witte
IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease
PNAS,
September 30, 2003;
100(20):
11630 - 11635.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Wertheim, S. A. Perera, D. A. Hammer, R. Ren, D. Boettiger, and W. S. Pear
Localization of BCR-ABL to F-actin regulates cell adhesion but does not attenuate CML development
Blood,
September 15, 2003;
102(6):
2220 - 2228.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. P. Huntly, A. Bench, and A. R. Green
Double jeopardy from a single translocation: deletions of the derivative chromosome 9 in chronic myeloid leukemia
Blood,
August 15, 2003;
102(4):
1160 - 1168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Wong, J. McLaughlin, D. Cheng, and O. N. Witte
Cell context-specific effects of the BCR-ABL oncogene monitored in hematopoietic progenitors
Blood,
May 15, 2003;
101(10):
4088 - 4097.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. E. Hirst, M. S. Buzza, C. H. Bird, H. S. Warren, P. U. Cameron, M. Zhang, P. G. Ashton-Rickardt, and P. I. Bird
The Intracellular Granzyme B Inhibitor, Proteinase Inhibitor 9, Is Up-Regulated During Accessory Cell Maturation and Effector Cell Degranulation, and Its Overexpression Enhances CTL Potency
J. Immunol.,
January 15, 2003;
170(2):
805 - 815.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Mayotte, D.-C. Roy, J. Yao, E. Kroon, and G. Sauvageau
Oncogenic interaction between BCR-ABL and NUP98-HOXA9 demonstrated by the use of an in vitro purging culture system
Blood,
December 1, 2002;
100(12):
4177 - 4184.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Jiang, E. Ng, C. Yip, W. Eisterer, Y. Chalandon, M. Stuible, A. Eaves, and C. J. Eaves
Primitive interleukin 3 null hematopoietic cells transduced with BCR-ABL show accelerated loss after culture of factor-independence in vitro and leukemogenic activity in vivo
Blood,
November 15, 2002;
100(10):
3731 - 3740.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. P. Huntly, A. J. Bench, E. Delabesse, A. G. Reid, J. Li, M. A. Scott, L. Campbell, J. Byrne, E. Pinto, A. Brizard, et al.
Derivative chromosome 9 deletions in chronic myeloid leukemia: poor prognosis is not associated with loss of ABL-BCR expression, elevated BCR-ABL levels, or karyotypic instability
Blood,
May 29, 2002;
99(12):
4547 - 4553.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. P. Million, J. Aster, D. G. Gilliland, and R. A. Van Etten
The Tel-Abl (ETV6-Abl) tyrosine kinase, product of complex (9;12) translocations in human leukemia, induces distinct myeloproliferative disease in mice
Blood,
May 29, 2002;
99(12):
4568 - 4577.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Holtz, M. L. Slovak, F. Zhang, C. L. Sawyers, S. J. Forman, and R. Bhatia
Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation
Blood,
May 15, 2002;
99(10):
3792 - 3800.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Wertheim, K. Forsythe, B. J. Druker, D. Hammer, D. Boettiger, and W. S. Pear
BCR-ABL-induced adhesion defects are tyrosine kinase-independent
Blood,
May 13, 2002;
99(11):
4122 - 4130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Chalandon, X. Jiang, G. Hazlewood, S. Loutet, E. Conneally, A. Eaves, and C. Eaves
Modulation of p210BCR-ABL activity in transduced primary human hematopoietic cells controls lineage programming
Blood,
May 1, 2002;
99(9):
3197 - 3204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. He, J. A. Wertheim, L. Xu, J. P. Miller, F. G. Karnell, J. K. Choi, R. Ren, and W. S. Pear
The coiled-coil domain and Tyr177 of bcr are required to induce a murine chronic myelogenous leukemia-like disease by bcr/abl
Blood,
April 15, 2002;
99(8):
2957 - 2968.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. M. F. Mow, J. Chandra, P. A. Svingen, C. G. Hallgren, E. Weisberg, T. J. Kottke, V. L. Narayanan, M. R. Litzow, J. D. Griffin, E. A. Sausville, et al.
Effects of the Bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on chronic myelogenous leukemia cells in vitro
Blood,
January 15, 2002;
99(2):
664 - 671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Kelly, Q. Liu, J. L. Kutok, I. R. Williams, C. L. Boulton, and D. G. Gilliland
FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myeloproliferative disease in a murine bone marrow transplant model
Blood,
January 1, 2002;
99(1):
310 - 318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Sinclair, J. A. Lee, A. Goldstein, D. Xing, S. Liu, R. Ju, P. W. Tucker, E. J. Neufeld, and R. H. Scheuermann
Lymphoid apoptosis and myeloid hyperplasia in CCAAT displacement protein mutant mice
Blood,
December 15, 2001;
98(13):
3658 - 3667.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. P. Huntly, A. G. Reid, A. J. Bench, L. J. Campbell, N. Telford, P. Shepherd, J. Szer, H. M. Prince, P. Turner, C. Grace, et al.
Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia
Blood,
September 15, 2001;
98(6):
1732 - 1738.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Karlic, N. Louda, M. Pfeilstocker, F. Keil, A. Lohninger, E. Pittermann, and J. Paukovits
Effect of the Hemoregulatory Peptide (pEEDCK)2 (pyroGlu-Glu-Asp-Cys-Lys)2 and MIP-1{alpha} is Reduced in Bone Marrow Cultures from Patients with Chronic Myeloid Leukemia (CML)
Stem Cells,
July 1, 2001;
19(4):
321 - 328.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
