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

Author:
  • Maria Askmyr
  • Helena Ågerstam
  • Henrik Lilljebjörn
  • Nils Hansen
  • Christine Karlsson
  • Sofia von Palffy
  • Niklas Landberg
  • Carl Högberg
  • Carin Lassen
  • Marianne Rissler
  • Johan Richter
  • Mats Ehinger
  • Marcus Järås
  • Thoas Fioretos
Publishing year: 2014
Language: English
Pages: 269-269
Publication/Series: Blood Cancer Journal
Volume: 4
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

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.

Keywords

  • Cancer and Oncology
  • Hematology

Other

Published
  • ISSN: 2044-5385
Thoas Fioretos
E-mail: thoas.fioretos [at] med.lu.se

Principal investigator

Division of Clinical Genetics

+46 46 222 45 95

+46 70 334 33 67

BMC C13

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