Myeloid Leukemia

Deletion of Derivative Chromosome 9 in CML 107
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Deletion of the Derivative Chromosome 9 in Chronic
Myeloid Leukemia
Lynda J. Campbell
Summary
With the development of fluorescence in situ hybridization (FISH), it was possible to detect
the BCR-ABL fusion signal in both metaphase spreads and interphase cells of patients with
chronic myeloid leukemia (CML). However, the use of FISH to detect residual disease in patients
with CML post therapy was limited by the false positive rate using the early single fusion
probes. Therefore, dual fusion probes that created a fusion signal on the derivative chromosome
9 in addition to the fusion sifnal on the Philadelphia chromosome or derivative chromosome
22 were developed. Using these second-generation probes, it was discovered that a
significant proportion of CML cases has a sub-microscopic deletion at the site of the ABL-BCR
fusion. This chapter outlines a testing strategy to identify deleltions of the derivative chromosome
9 and to use combinations of probes to identify residual disease in these cases.
Key Words: Cytogenetic; karyotype; interstitial deletion; fluorescence in situ hybridization;
BCR; ABL; derivative chromosome.
1. Introduction
The hallmark discoveries of the genetics of chronic myeloid leukemia
(CML) have mirrored the evolution of the fields of cytogenetics and molecular
genetics. CML was first recognized as a distinct entity in 1845, but it was not
until 1960, when Nowell and Hungerford identified a small marker chromosome
(known as the Philadelphia chromosome) in the blood of patients with
CML, that cancer cytogenetics was born. The abnormality was identified as a
reciprocal translocation between chromosomes 9 and 22 by Janet Rowley in
1973. Subsequently, the underlying genetic events were described in the 1980s,
with the translocation found to produce a fusion gene, BCR-ABL, at the site of
the breakpoint on the derivative chromosome 22, der(22) (1). It was also established
that the single translocation event produced two fusion genes, a BCR-
From: Methods in Molecular Medicine, Vol. 125: Myeloid Leukemia: Methods and Protocols
Edited by: H. Iland, M. Hertzberg, and P. Marlton © Humana Press Inc., Totowa, NJ
107