Dissection of the Pathogenesis of Neurofibromatosis Type 1-Associated myeloid Leukemia.
Annual rept. 19 Sep 97-18 Sep 98
FLORIDA UNIV GAINESVILLE
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Although most of the tumors associated with neurofibromatosis type 1 NFl are benign in nature, malignant transformation of a subset of NFl tumors is a serious complication, often leading to the death of the patient. This is true for NFl -associated juvenile chronic myelogenous leukemia JCML, known to progress into acute leukemia. Our goal is to investigate the events which lead to the transformation and leukemic progression of NFl-associated JCML using a mouse model that we have ja developed. This model system takes advantage of transgenic mice that harbor one mutant allele of the Nfl gene, but require further mutations for transformation. This past year, we have backcrossed this mutant Nfi allele for three generations to a strain of mouse that expresses a murine leukemia virus MuLV. In this system, the MuLV acts as a mutagen to activate cooperating cellular proto-oncogenes or inactivate tumor suppressor genes, resulting in accelerated tumor development. So far, we have been able to generate 17 new tumors to add to our panel and have many other animals in aging. Furthermore, we have initiated experiments directed at cloning the affected genes based on their proximity to the newly integrated proviral DNA.
- Medicine and Medical Research