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Leukemia Initiated by Hemopoietic Stem Cells Expressing the v-abl Oncogene
Siu-Wah Chung, Peter M. C. Wong, Helen Durkin, Yue-Sheng Wu and Joan Petersen
Proceedings of the National Academy of Sciences of the United States of America
Vol. 88, No. 4 (Feb. 15, 1991), pp. 1585-1589
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/2356041
Page Count: 5
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We report a mouse model with which to study leukemogenesis initiated by a specific genetic change introduced into a primary lymphoid-myeloid pluripotent stem cell. Fetal liver hemopoietic cells were infected with a high titer of helper-free Abelson murine leukemia virus (A-MuLV) and were used to reconstitute lethally irradiated mice. Two weeks later, progenies of a single primitive hemopoietic stem cell carrying a specifically integrated A-MuLV proviral DNA could be detected in both colony-forming units in spleen and myeloid colony-forming cells in the bone marrow. Beginning at 3 weeks after transplantation, the recipients developed elevated leukocyte counts, splenomegaly, and increase of blast cells in the peripheral blood. Multiple clones of A-MuLV-infected cells were infused into each recipient. However, in the same animal, DNA extracted from various affected organs and from factor-independent lymphoid and myeloid immortalized cells all contained an identical, specifically integrated proviral genome. The A-MuLV-infected stem cells differentiated into various lineages of hemopoietic cells. Our data show that the expression of the v-abl oncogene in a primary lymphoid-myeloid hemopoietic stem cell directly initiates leukemogenesis by stimulating factor-independent growth. The monoclonal-type disease development seen in these animals may require the occurrence of an additional genetic event.
Proceedings of the National Academy of Sciences of the United States of America © 1991 National Academy of Sciences