Analysis of expansion of myeloid progenitors in mice to identify leukemic susceptibility genes |
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Authors: | Vincent E Sollars Ed Pequignot Jay L Rothstein Arthur M Buchberg |
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Institution: | (1) Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA;(2) Department of Medicine, Division of Clinical Pharmacology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA;(3) Department of Otolaryngology-Head and Neck Surgery, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th Street, Philadelphia, Pennsylvania 19107, USA;(4) Present address: Department of Microbiology, Immunology, and Molecular Genetics, Joan C. Edwards School of Medicine, Marshall University, 1542 Spring Valley Drive, Huntington, WV 25704, USA |
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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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