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 Previous Article | Table of Contents | Next Article 
The balanced and the unbalanced chromosome aberrations of acute myeloid
leukemia may develop in different ways and may contribute differently to
malignant transformation
J Pedersen-Bjergaard and JD Rowley
Department of Hematology L 4132, Rigshospitalet, Copenhagen, Denmark.
Two general types of clonal chromosome abnormality are observed in de novo
acute myeloid leukemia (AML): the unbalanced aberrations with visible gain
or loss of chromosome material and the balanced aberrations without such
visible gain or loss. AML can be induced by therapy with cytostatic drugs
and radiation. The alkylating agents reacting directly with DNA induce AML
which often presents as myelodysplasia with unbalanced aberrations,
primarily loss of chromosome material. Cytostatic agents targeting
DNA-topoisomerase II, frequently administered together with alkylating
agents or cisplatin, induce the same type of leukemia. In addition, they
often induce another type with a more rapid onset and with specific
balanced chromosome aberrations rarely observed after therapy with
alkylating agents alone. All of the most important chromosome aberrations
found in de novo AML are now also found in therapy-related AML (t-AML);
thus, t- AML may serve as a model in the search for mechanisms leading to
the development of AML in general. Unbalanced chromosome aberrations with
partial deletions or with loss of whole chromosomes may develop as a result
of alkylation of DNA or other cellular targets. Balanced chromosome
aberrations, on the other hand, may develop as illegitimate recombinations
related to the activity of DNA-topoisomerase II. The balanced
translocations contribute to malignant transformation by the formation of
abnormal chimeric genes, whereas deletions may contribute by the loss of
putative tumor suppressor genes. In either situation, the chromosome
changes provide the altered cells with a proliferative advantage compared
with normal cells.
Volume 83,
Issue 10,
pp. 2780-2786,
05/15/1994
Copyright © 1994 by The American Society of Hematology
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