MUTATIONS WITHIN THE FLR EXON OF NF1 ARE RARE IN MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOCYTIC LEUKEMIAS

A mutational hotspot in the neurofibromatosis 1 (NF1) gene has recentl y emerged from the analysis of different malignancies including one pa tient with myelodysplastic syndrome (MDS). in these cases, Lys 1423 in the GTPase-activating protein (GAP)-related domain of NF1 is substitu ted which causes a significant reduction of intrinsic GAP activity. We studied 57 MDS patients and 27 cases of acute myelocytic leukemia (AM L) for mutations at codon 1423 in the so-called FLR exon of NF1 by an assay based on restriction enzyme digestion. We investigated the entir e FLR exon and its flanking intron sequences using single-strand confo rmation polymorphism (SSCP) analysis of polymerase chain reaction (PCR ) products and sequencing. None of the cases exhibited a codon 1423 mu tation. However, a patient with chronic myelomonocytic leukemia (CMML) showed a 3 bp deletion within the splice acceptor region in front of the FLR exon. These data suggest that NF1 exon FLR mutations contribut e infrequently to the development of MDS and AML.