Internal tandem duplication, d835 mutation in acute myeloid and promielocitic leukemia

Introduction. Biological characteristics and prognostic values of FMS-like kinasi 3 (FLT3) gene dislocated on 13q12 were studied. This protein is employed in staminal and B cell differentiation. Mutations of FLT3 are present in 35- 40% of patients with acute myeloid leukaemia. These genetic alterations consist of “Internal tandem duplications” (ITDs) and substitution of aspartic acid (Asp) in the 835 positions. Aims of study The aim of this study was to individuate a diagnostic method for FLT3/ITDs and D835 mutation. Materials and methods. From January 2004, 34 consecutive cases with de novo Acute Myeloid Leukemia (AML) have been studied. Median age was 50 years (range 25 – 80). Twenty-three case were male and 11 female. Two PCR methods have been used for FLT3/ITDs and one for D835 mutations. Mixed lineage leukemia gene (MLL) study and t(9,22)p190, t(9,22)p210, t(8;21), t(4;11) translocations analyses have been performed. Study of sequence gene were made in Leukaemia Frankfurt Institute. Were utilised a set of new primers dislocated between 10/11 and 12/13 exons of FLT3 gene Results. In 11/34 (34,4%) cases, FLT3/ITDs transcripts were positives by RT-PCR. In only two cases, FLT3/ITDs positives was confirmed with sequence analysis. In 2/11 positive cases (18,1%) were revealed base substitutions butnot specific mutations in FLT3 gene. MLL studies and specific AML translocations were negative on all cases. D835 mutations by exon 17 were positives on 2 cases (5,8%). Conclusions The new primers set, for exon 11/12; 12/13 in FLT3/ITDs gene, had given results confirmed by sequence analysi