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

L. M. Rimsza, K. J. Kopecky, J. Ruschulte, I. M. Chen, M. L. Slovak, C. Karanes, J. Godwin, A. List, C. L. Willman

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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 leukemia 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.

Original languageEnglish (US)
Pages (from-to)1044-1051
Number of pages8
JournalLeukemia
Volume14
Issue number6
DOIs
StatePublished - Jan 1 2000

Keywords

  • Acute myelogenous leukemia
  • DNA repair
  • Microsatellite instability
  • Secondary leukemia
  • Theraphy-induced leukemia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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