Originally published as JCO Early Release 10.1200/JCO.2008.16.0259 on August 11 2008

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Monosomal Karyotype in Acute Myeloid Leukemia: A Better Indicator of Poor Prognosis Than a Complex Karyotype

Dimitri A. Breems, Wim L.J. Van Putten, Georgine E. De Greef, Shama L. Van Zelderen-Bhola, Klasien B.J. Gerssen-Schoorl, Clemens H.M. Mellink, Aggie Nieuwint, Martine Jotterand, Anne Hagemeijer, H. Berna Beverloo, Bob Löwenberg

From the Department of Hematology, Hospital Network Antwerp, Campus Stuivenberg, Antwerp; Center for Human Genetics, University of Leuven, Leuven, Belgium; Dutch-Belgian Hemato-Oncology Cooperative Group Data Center; Departments of Trials and Statistics, Hematology, and Clinical Genetics, Erasmus University Medical Center, Rotterdam; Department of Clinical Genetics, Free University Medical Center; Department of Clinical Genetics, Institute for Human Genetics, Academic Medical Center, Amsterdam; Department of Genetics, University Medical Center, Groningen, the Netherlands; and Unit of Cancer Cytogenetics, Department of Medical Genetics, University Hospital Center Vaudois, Lausanne, Switzerland

Corresponding author: Bob Löwenberg, MD, PhD, Department of Hematology, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands; e-mail: b.lowenberg{at}erasmusmc.nl

Purpose To investigate the prognostic value of various cytogenetic components of a complex karyotype in acute myeloid leukemia (AML).

Patients and Methods Cytogenetics and overall survival (OS) were analyzed in 1,975 AML patients age 15 to 60 years.

Results Besides AML with normal cytogenetics (CN) and core binding factor (CBF) abnormalities, we distinguished 733 patients with cytogenetic abnormalities. Among the latter subgroup, loss of a single chromosome (n = 109) conferred negative prognostic impact (4-year OS, 12%; poor outcome). Loss of chromosome 7 was most common, but outcome of AML patients with single monosomy –7 (n = 63; 4-year OS, 13%) and other single autosomal monosomies (n = 46; 4-year OS, 12%) did not differ. Structural chromosomal abnormalities influenced prognosis only in association with a single autosomal monosomy (4-year OS, 4% for very poor v 24% for poor). We derived a monosomal karyotype (MK) as a predictor for very poor prognosis of AML that refers to two or more distinct autosomal chromosome monosomies (n = 116; 4-year OS, 3%) or one single autosomal monosomy in the presence of structural abnormalities (n = 68; 4-year OS, 4%). In direct comparisons, MK provides significantly better prognostic prediction than the traditionally defined complex karyotype, which considers any three or more or five or more clonal cytogenetic abnormalities, and also than various individual specific cytogenetic abnormalities (eg, del[5q], inv[3]/t[3;3]) associated with very poor outcome.

Conclusion MK enables (in addition to CN and CBF) the prognostic classification of two new aggregates of cytogenetically abnormal AML, the unfavorable risk MK-negative category (4-year OS, 26% ± 2%) and the highly unfavorable risk MK-positive category (4-year OS, 4% ± 1%).

published online ahead of print at www.jco.org on August 11, 2008

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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