Mammalian Genome

, Volume 17, Issue 8, pp 808–821 | Cite as

Analysis of expansion of myeloid progenitors in mice to identify leukemic susceptibility genes

  • Vincent E. Sollars
  • Ed Pequignot
  • Jay L. Rothstein
  • Arthur M. Buchberg
Original Contributions

Abstract

The myeloid progenitor cell compartment (MPC) exhibits pronounced expansion in human myeloid leukemias. It is becoming more apparent that progression of myelodysplastic syndromes and myeloproliferative diseases to acute myelogenous leukemia is the result of defects in progenitor cell maturation. The MPC of bone marrow was analyzed in mice using a cell culture assay for measuring the relative frequency of proliferative myeloid progenitors. Response to the cytokines SCF, IL-3, and GM-CSF was determined by this assay for the leukemic mouse strain BXH-2 and ten other inbred mouse strains. Significant differences were found to exist among ten inbred mouse strains in the nature of their MPC in bone marrow, indicating the presence of genetic polymorphisms responsible for the divergence. The SWR/J and FVB/J strains show consistently low frequencies of myeloid progenitors, while the DBA/2J and SJL/J inbred strains show consistently high frequencies of myeloid progenitors within the bone marrow compartment. In addition, in silico linkage disequilibrium analysis was conducted to identify possible chromosomal regions responsible for the phenotypic variation. Given the importance of this cell compartment in leukemia progression and the soon to be released genomic sequence of 15 mouse strains, these differences may provide a valuable tool for research into leukemia.

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Vincent E. Sollars
    • 1
    • 4
  • Ed Pequignot
    • 2
  • Jay L. Rothstein
    • 3
  • Arthur M. Buchberg
    • 1
  1. 1.Department of Microbiology and Immunology, Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaUSA
  2. 2.Department of Medicine, Division of Clinical Pharmacology, Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaUSA
  3. 3.Department of Otolaryngology-Head and Neck Surgery, Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaUSA
  4. 4.Department of Microbiology, Immunology, and Molecular GeneticsJoan C. Edwards School of Medicine, Marshall UniversityHuntingtonUSA

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