ANALYSIS OF NEUROFIBROMATOSIS TYPE-1 GENE MUTATION IN JUVENILE CHRONIC MYELOGENOUS LEUKEMIA

The neurofibromatosis type 1 (NF1) gene has been considered to be a tu mor suppressor gene, since the NF1 gene product downregulates the ras oncogene product (p21(ras)). In addition, children with NF1 show an in creased incidence of myelogenous leukemia, including juvenile chronic myelogenous leukemia (JCML). We studied 8 Japanese JCML patients witho ut NF I for mutations in exons 21-36 of the NF1 gene by using polymera se chain reaction/single-strand conformation polymorphism analysis. Th is region was chosen because it includes two main hotspots in the NF1 gene as well as the functionally important domain, GTPase-activating p rotein-related domain, which mediates the downregulation of ras activi ty. One of the 8 JCML patients exhibited a G to T transversion at the third nucleotide of the codon GAG for Glu at amino acid residue 1699, which results in the heterozygous conversion to Asp (E1699D). This var iation was detected neither in 65 healthy volunteers nor 50 NF1 patien ts. No other variations were detected in our JCML patients. We suggest that NF1 gene mutation does not occur frequently in JCML without NF1.