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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

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

Summary, in 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.

Department/s

  • Division of Molecular Medicine and Gene Therapy
  • Division of Clinical Genetics
  • Tumor microenvironment
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy

Publishing year

2014

Language

English

Publication/Series

Blood Cancer Journal

Volume

4

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology
  • Hematology

Status

Published

ISBN/ISSN/Other

  • ISSN: 2044-5385