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MDS and Cytogenetics

Increased frequency of dicentric chromosomes in therapy-related MDS and AML compared to de novo disease is significantly related to previous treatment with alkylating agents and suggests a specific susceptibility to chromosome breakage at the centromere

Leukemia volume 14, pages 105–111 (2000)Cite this article

Abstract

Dicentric chromosomes are observed in many malignant diseases including myelodysplasia (MDS) and acute myeloid leukemia (AML) and have often been observed in a subset of these diseases, namely therapy-related MDS (t-MDS) and AML (t-AML). Using fluorescence in situ hybridization (FISH) with centromere-specific probes, we investigated the frequency and type of dicentric chromosomes in 180 consecutive patients with t-MDS and t-AML and in 231 consecutive patients with de novo MDS and AML, whose karyotypes had been studied previously by conventional G-banding. Twenty-seven out of 180 patients with t-MDS or t-AML presented dicentric chromosomes compared to only seven out of 231 patients with de novo disease (P = 0.00003). A dic(1q;7p) was observed in 10 cases, a dic(5p;17q) was observed in six cases, whereas various isodicentric chromosomes were observed in six cases. Excluding these six cases with isodicentrics, all 25 patients with dicentric chromosomes had involvement of at least one of the chromosome arms 1q, 5p, or 7p resulting in monosomy for 5q or 7q, and/or trisomy for 1q. Patients with dicentric chromosomes presented significantly more often as t-MDS compared to patients without dicentrics (P = 0.046), and the presence of a dicentric chromosome was significantly related to previous therapy with alkylating agents (P = 0.026). Thus, only one out of 27 patients with a dicentric chromosome had not previously received an alkylating agent. A specific susceptibility to breakage at the centromere after exposure to alkylating agents is suggested and may explain the frequent loss of whole chromosomes, in particular chromosomes 5 and 7 in t-MDS and t-AML, if the breaks are not followed by rejoining.

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Acknowledgements

This work was supported by grants from HS forskningspulje 1997, the Danish Cancer Society, and Anders Hasselbalchs fond til leukaemiers bekaempelse. We are indebted to lnge-lise Frost Andersen for excellent and careful technical assistance in performing the FISH analyses, and to Harry Cowan for help in the preparation of the manuscript.

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  1. Chromosome Laboratory, Section 5702, The Juliane Marie Center, Rigshospitalet, Henrik Harpestrengsvej 4, Copenhagen Ø, 2100, Denmark

    MK Andersen & J Pedersen-Bjergaard

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Andersen, M., Pedersen-Bjergaard, J. Increased frequency of dicentric chromosomes in therapy-related MDS and AML compared to de novo disease is significantly related to previous treatment with alkylating agents and suggests a specific susceptibility to chromosome breakage at the centromere. Leukemia 14, 105–111 (2000). https://doi.org/10.1038/sj.leu.2401594

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