Dissection of the Pathogenesis of Neurofibromatosis Type 1-Associated Myeloid Leukemia
Abstract
Although most of the tumors associated with neurofibromatosis type 1 (NF1) are benign in nature, malignant transformation of a subset of NF1 tumors is a serious complication, often leading to the death of the patient. This is true for NF 1-associated juvenile chronic myelogenous leukemia (JCML), known to progress into acute myeloid leukemia (AML). Previously,we have shown that loss of Nfl in the hematopoetic lineage results in JCML. The goal of this grant is to idertify the genetic events which lead to the transformation and leukemic progression of NF1-associated JCML using a mouse model. This model system takes advantage of transgenic mice that harbor one mutant allele of the Nfl gene, but require further mutations for transformation. We have backcrossed this mutant Nfl 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, by cloning sites of somatic MuLV integration from tumor DNAs obtained from these backcrossed mice, we have identified two genes that appear to cooperate with the loss of Nfl to cause to AML.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA385904
Entities
People
- Camilynn I. Brannan
Organizations
- University of Florida