Microsatellite instability is not a defining genetic feature of acute myeloid leukemogenesis in adults: results of a retrospective study of 132 patients and review of the literature

The frequency of acute leukemia in children with constitutional DNA repair defects implicates defective DNA repair in leukemogenesis. Whether sporadic cases of AML also arise from an inherited genetic predisposition remains t o be determined. Prior studies have reported microsatellite instability (MS I) in AML, particularly secondary and relapsed AML. These studies included small numbers of cases in which key features such as cytogenetic abnormalit ies were not reported. To determine whether defective DNA mismatch repair, reflected by MSI, is a defining feature of adult myeloid leukemogenesis, we retrospectively studied 132 AML cases including 28 de novo, 62 secondary, 22 relapsed/refractory, 15 cases of paired diagnosis/relapse. 110 patients were elderly (55+ years). The cases included a range of cytogenetic abnorma lities. MSI was assessed at three loci (BAT 25, BAT 26, BAT 40) in DNA isol ated from sorted leukemic blasts and paired T cell controls. Fluoresceinate d PCR products were analyzed using an automated capillary electrophoresis s ystem. Of the 132 AML cases, no single case demonstrated MSI. Our studies i ndicate that MSI, and defective DNA mismatch repair, is not a defining feat ure of the majority of adult patients with AML. Furthermore, our data does not support the hypothesis that MSI could be acquired during the progressio n of AML from diagnosis to relapse, as a consequence of therapeutic exposur e.