¹Department of Pathology and Cancer Center, University of New Mexico, Albuquerque, NM, USA

²Fred Hutchinson Cancer Research Center and Southwest Oncology Group Statistical Center, Seattle, WA, USA

³Department of Cytogenetics, City of Hope National Medical Center, Duarte, CA, USA

⁴Department of Internal Medicine, Wayne State University, Detroit, MI, USA

⁵Loyola University Chicago, Maywood, IL, USA

⁶University of Arizona Cancer Center, Bone Marrow Transplant Program, Tucson, AZ, USA

Correspondence to: C Willman, Cancer Research Facility, University of New Mexico School of Medicine, 2325 Camino de Salud NE, Albuquerque, NM 87131-5636, USA

^aPresent address: Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA

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 to be determined. Prior studies have reported microsatellite instability (MSI) in AML, particularly secondary and relapsed AML. These studies included small numbers of cases in which key features such as cytogenetic abnormalities 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 abnormalities. MSI was assessed at three loci (BAT 25, BAT 26, BAT 40) in DNA isolated from sorted leukemic blasts and paired T cell controls. Fluoresceinated PCR products were analyzed using an automated capillary electrophoresis system. Of the 132 AML cases, no single case demonstrated MSI. Our studies indicate that MSI, and defective DNA mismatch repair, is not a defining feature of the majority of adult patients with AML. Furthermore, our data does not support the hypothesis that MSI could be acquired during the progression of AML from diagnosis to relapse, as a consequence of therapeutic exposure. Leukemia (2000) 14, 1044-1051.

acute myelogenous leukemia; secondary leukemia; therapy-induced leukemia; microsatellite instability; DNA repair