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

Lisa 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 Citations (Scopus)

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
StatePublished - 2000
Externally publishedYes

Fingerprint

Microsatellite Instability
Retrospective Studies
DNA Mismatch Repair
Chromosome Aberrations
DNA Repair
Leukemia
Recurrence
Capillary Electrophoresis
Genetic Predisposition to Disease
T-Lymphocytes
Polymerase Chain Reaction
DNA

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

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

In: Leukemia, Vol. 14, No. 6, 2000, p. 1044-1051.

Research output: Contribution to journalArticle

Rimsza, LM, Kopecky, KJ, Ruschulte, J, Chen, IM, Slovak, ML, Karanes, C, Godwin, J, List, A & Willman, CL 2000, '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', Leukemia, vol. 14, no. 6, pp. 1044-1051.
Rimsza, Lisa M ; Kopecky, K. J. ; Ruschulte, J. ; Chen, I. M. ; Slovak, M. L. ; Karanes, C. ; Godwin, J. ; List, A. ; Willman, C. L. / 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. In: Leukemia. 2000 ; Vol. 14, No. 6. pp. 1044-1051.
@article{9b703d959b084a929263dd8e20a58b73,
title = "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",
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.",
keywords = "Acute myelogenous leukemia, DNA repair, Microsatellite instability, Secondary leukemia, Theraphy-induced leukemia",
author = "Rimsza, {Lisa M} and Kopecky, {K. J.} and J. Ruschulte and Chen, {I. M.} and Slovak, {M. L.} and C. Karanes and J. Godwin and A. List and Willman, {C. L.}",
year = "2000",
language = "English (US)",
volume = "14",
pages = "1044--1051",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Microsatellite instability is not a defining genetic feature of acute myeloid leukemogenesis in adults

T2 - Results of a retrospective study of 132 patients and review of the literature

AU - Rimsza, Lisa M

AU - Kopecky, K. J.

AU - Ruschulte, J.

AU - Chen, I. M.

AU - Slovak, M. L.

AU - Karanes, C.

AU - Godwin, J.

AU - List, A.

AU - Willman, C. L.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - Acute myelogenous leukemia

KW - DNA repair

KW - Microsatellite instability

KW - Secondary leukemia

KW - Theraphy-induced leukemia

UR - http://www.scopus.com/inward/record.url?scp=0034123441&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034123441&partnerID=8YFLogxK

M3 - Article

VL - 14

SP - 1044

EP - 1051

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 6

ER -