|Budget Amount *help
¥13,300,000 (Direct Cost : ¥13,300,000)
Fiscal Year 2003 : ¥6,400,000 (Direct Cost : ¥6,400,000)
Fiscal Year 2002 : ¥6,900,000 (Direct Cost : ¥6,900,000)
Chronic myelogenous leukemia (CML) is a clonal disorder of hematopoietic stem cells transformed by p210BCR/ABL, characterized by excessive and uncontrolled proliferation of myeloid cells. Clinically it begins as an indolent chronic phase, but inevitably accelerates and finally progresses into a fatal blast crisis, which resembles acute leukemia. Although additional genetic change(s) is considered to contribute to the blast crisis of CML, underlying molecular mechanism(s) has remained unclear.
We have developed transgenic mice expressing p210BCR/ABL using a promoter of a gene preferentially expressed in hematopoietic precursor cells. The transgenic mice reproducibly exhibited a myeloproliferative disorder closely resembling human CML, allowing us to consider that the transgenic mice to be an excellent animal model for human CML. Using this transgenic model as a tool, we have been attempting to identify genes responsible for progression of CML. To this aim, we did "in vivo mutagenesis" by infecting retroviruses into CML transgenic mice. BHX2, a mouse strain which transmits retroviruses through milk (Nature Genet. 23, 348-53, 1999), is used for this study. We crossmated p210BCR/ABL transgenic mice with BXH2 mice and backcrossed the mice to BXH2 for three times to have BXH2 genetic background. We have been examining the cell count and cell smear of pheripheral blood of the mice. So far, we have found 3 mice that developed acute leukemia. We will continue this study and when we have enough number of mice that exhibited acute leukemia, we isolate DNA from leukemic samples and identify genes responsible for blast crisis of CML by PCR using virus-specific primers.