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Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow.

Publication ,  Journal Article
Pear, WS; Miller, JP; Xu, L; Pui, JC; Soffer, B; Quackenbush, RC; Pendergast, AM; Bronson, R; Aster, JC; Scott, ML; Baltimore, D
Published in: Blood
November 15, 1998

Expression of the 210-kD bcr/abl fusion oncoprotein can cause a chronic myelogenous leukemia (CML)-like disease in mice receiving bone marrow cells transduced by bcr/abl-encoding retroviruses. However, previous methods failed to yield this disease at a frequency sufficient enough to allow for its use in the study of CML pathogenesis. To overcome this limitation, we have developed an efficient and reproducible method for inducing a CML-like disease in mice receiving P210 bcr/abl-transduced bone marrow cells. All mice receiving P210 bcr/abl-transduced bone marrow cells succumb to a myeloproliferative disease between 3 and 5 weeks after bone marrow transplantation. The myeloproliferative disease recapitulates many of the hallmarks of human CML and is characterized by high white blood cell counts and extensive extramedullary hematopoiesis in the spleen, liver, bone marrow, and lungs. Use of a retroviral vector coexpressing P210 bcr/abl and green fluorescent protein shows that the vast majority of bcr/abl-expressing cells are myeloid. Analysis of the proviral integration pattern shows that, in some mice, the myeloproliferative disease is clonal. In multiple mice, the CML-like disease has been transplantable, inducing a similar myeloproliferative syndrome within 1 month of transfer to sublethally irradiated syngeneic recipients. The disease in many of these mice has progressed to the development of acute lymphoma/leukemia resembling blast crisis. These results demonstrate that murine CML recapitulates important features of human CML. As such, it should be an excellent model for addressing specific issues relating to the pathogenesis and treatment of this disease.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

November 15, 1998

Volume

92

Issue

10

Start / End Page

3780 / 3792

Location

United States

Related Subject Headings

  • Virus Integration
  • Transfection
  • Splenomegaly
  • Retroviridae
  • Reproducibility of Results
  • Recombinant Fusion Proteins
  • Radiation Chimera
  • Proviruses
  • Oncogenes
  • Neoplasm Transplantation
 

Citation

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Pear, W. S., Miller, J. P., Xu, L., Pui, J. C., Soffer, B., Quackenbush, R. C., … Baltimore, D. (1998). Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow. Blood, 92(10), 3780–3792.
Pear, W. S., J. P. Miller, L. Xu, J. C. Pui, B. Soffer, R. C. Quackenbush, A. M. Pendergast, et al. “Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow.Blood 92, no. 10 (November 15, 1998): 3780–92.
Pear WS, Miller JP, Xu L, Pui JC, Soffer B, Quackenbush RC, et al. Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow. Blood. 1998 Nov 15;92(10):3780–92.
Pear WS, Miller JP, Xu L, Pui JC, Soffer B, Quackenbush RC, Pendergast AM, Bronson R, Aster JC, Scott ML, Baltimore D. Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow. Blood. 1998 Nov 15;92(10):3780–3792.

Published In

Blood

ISSN

0006-4971

Publication Date

November 15, 1998

Volume

92

Issue

10

Start / End Page

3780 / 3792

Location

United States

Related Subject Headings

  • Virus Integration
  • Transfection
  • Splenomegaly
  • Retroviridae
  • Reproducibility of Results
  • Recombinant Fusion Proteins
  • Radiation Chimera
  • Proviruses
  • Oncogenes
  • Neoplasm Transplantation