Neurofibromatosis type 1 (NF1) gene is a tumor suppressor gene, and the NF1 gene product, neurofibromin, can downregulate the N-ras gene. Because the N-ras gene is often mutated in acute myelogenous leukemia (AML), we wondered if the NF1 gene might be mutated in those AML samples not having N-ras mutations. We investigated the mutational status of the N-ras gene and the FLR exon of codons 1371-1423 of the open reading frame of the full-length NF1 cDNA, which has a strong homology with the mammalian ras GTPase-activating protein (GAP), especially for a stretch of three consecutive amino acids (F, L, R), by single-strand conformation polymorphism analysis and direct sequencing in samples from patients with AML. Of 48 AML patients, 10 (21%) had point (missense) mutations of the N-ras gene involving codons 12, 13 and 61. However, mutations in the FLR exon of the NF1 gene were not detected in any of the AML samples. We also examined the difference of clinical response to induction therapy between AML patients with and without N-ras mutation. A significantly lower rate of complete remission was noted in individuals with N-ras gene mutations. These results suggest that mutation of the NF1 gene, at least in the FLR exon, is very rare in AML and the NF1 gene probably is not a functional complement of the N-ras gene mutation. The presence of N-ras gene mutation may be associated with a lower clinical response to antileukemic therapy.

Japanese Erwinia pyrifoliae strains cause bacterial shoot blight of pear (BSBP) in Japan. The genetics of Japanese Erwinia remains largely unknown relative to the abundant genomic information available for other Erwinia strains. We compared the genome of Japanese and Korean E. pyrifoliae strains along with those of E. amylovora and E. tasmaniensis. Comparisons with the Korean E. pyrifoliae strain revealed numerous gene insertions/deletions, rearrangements, and inversions in the central regions of the chromosomes. Approximately 80% (2843) of coding DNA sequences (CDSs) are shared by these two genomes which represent about three-quarters of the genome, and there are about 20% unique CDSs. Comparative analysis with closely related erwinias showed that 1942 (more than 50%) core open reading frames (ORF) are shared by all these strains. In addition to two type III secretion systems (hrp/dsp and inv/spa), the genome of Ejp617 encodes numerous virulence factors, including a type VI secretion system, an exopolysaccharide synthesis cluster, and another protein secretion system present in plant pathogenic Erwinia strains. The availability of whole genome sequence should provide a resource to further improve the understanding of pathogenesis in Japanese E. pyrifoliae Ejp617 and to facilitate evolutionary studies among the species of the genus Erwinia.