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Modeling chronic myeloid leukemia in immunodeficient mice reveals expansion of aberrant mast cells and accumulation of pre-B cells.

Askmyr, Maria LU ; Ågerstam, Helena LU ; Lilljebjörn, Henrik LU ; Hansen, Nils LU ; Karlsson, Christine LU ; von Palffy, Sofia LU ; Landberg, Niklas LU ; Högberg, Carl LU ; Lassen, Carin LU and Rissler, Marianne LU , et al. (2014) In Blood Cancer Journal 4. p.269-269
Abstract
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that, if not treated, will progress into blast crisis (BC) of either myeloid or B lymphoid phenotype. The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC. To generate a humanized CML model, we retrovirally expressed BCR-ABL1 in the cord blood CD34(+) cells and transplanted these into NOD-SCID (non-obese diabetic/severe-combined immunodeficient) interleukin-2-receptor γ-deficient mice. In primary mice, BCR-ABL1 expression induced an inflammatory-like state in the bone marrow and spleen, and mast cells were the only... (More)
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that, if not treated, will progress into blast crisis (BC) of either myeloid or B lymphoid phenotype. The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC. To generate a humanized CML model, we retrovirally expressed BCR-ABL1 in the cord blood CD34(+) cells and transplanted these into NOD-SCID (non-obese diabetic/severe-combined immunodeficient) interleukin-2-receptor γ-deficient mice. In primary mice, BCR-ABL1 expression induced an inflammatory-like state in the bone marrow and spleen, and mast cells were the only myeloid lineage specifically expanded by BCR-ABL1. Upon secondary transplantation, the pronounced inflammatory phenotype was lost and mainly human mast cells and macrophages were found in the bone marrow. Moreover, a striking block at the pre-B-cell stage was observed in primary mice, resulting in an accumulation of pre-B cells. A similar block in B-cell differentiation could be confirmed in primary cells from CML patients. Hence, this humanized mouse model of CML reveals previously unexplored features of CP CML and should be useful for further studies to understand the disease pathogenesis of CML. (Less)
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Blood Cancer Journal
volume
4
pages
269 - 269
publisher
Nature Publishing Group
external identifiers
  • pmid:25501026
  • wos:000347841000008
  • scopus:84927934542
ISSN
2044-5385
DOI
10.1038/bcj.2014.89
language
English
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yes
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817c071a-49ad-4475-b381-5c6067935e5a (old id 4908422)
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http://www.ncbi.nlm.nih.gov/pubmed/25501026?dopt=Abstract
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2015-01-11 19:32:56
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2017-10-22 04:01:32
@article{817c071a-49ad-4475-b381-5c6067935e5a,
  abstract     = {Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that, if not treated, will progress into blast crisis (BC) of either myeloid or B lymphoid phenotype. The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC. To generate a humanized CML model, we retrovirally expressed BCR-ABL1 in the cord blood CD34(+) cells and transplanted these into NOD-SCID (non-obese diabetic/severe-combined immunodeficient) interleukin-2-receptor γ-deficient mice. In primary mice, BCR-ABL1 expression induced an inflammatory-like state in the bone marrow and spleen, and mast cells were the only myeloid lineage specifically expanded by BCR-ABL1. Upon secondary transplantation, the pronounced inflammatory phenotype was lost and mainly human mast cells and macrophages were found in the bone marrow. Moreover, a striking block at the pre-B-cell stage was observed in primary mice, resulting in an accumulation of pre-B cells. A similar block in B-cell differentiation could be confirmed in primary cells from CML patients. Hence, this humanized mouse model of CML reveals previously unexplored features of CP CML and should be useful for further studies to understand the disease pathogenesis of CML.},
  author       = {Askmyr, Maria and Ågerstam, Helena and Lilljebjörn, Henrik and Hansen, Nils and Karlsson, Christine and von Palffy, Sofia and Landberg, Niklas and Högberg, Carl and Lassen, Carin and Rissler, Marianne and Richter, Johan and Ehinger, Mats and Järås, Marcus and Fioretos, Thoas},
  issn         = {2044-5385},
  language     = {eng},
  pages        = {269--269},
  publisher    = {Nature Publishing Group},
  series       = {Blood Cancer Journal},
  title        = {Modeling chronic myeloid leukemia in immunodeficient mice reveals expansion of aberrant mast cells and accumulation of pre-B cells.},
  url          = {http://dx.doi.org/10.1038/bcj.2014.89},
  volume       = {4},
  year         = {2014},
}