Title:On the Power of Additional and Complex Chromosomal Aberrations in CML
Volume: 13
Issue: 6
Author(s): Karin M. Greulich-Bode and Barbara Heinze
Affiliation:
Keywords:
CML, Cytogenetics, Fish, CGH translocation, Breakpoints, Complex aberrations, Clinical impact, clonal, complex karyotypes, the BCR-ABL fusion
Abstract: Unregulated proliferation of mainly myeloid bone marrow cells and genetic changes in the hematopoietic stem
cell system are important features in Chronic Myeloid Leukemia (CML). In clinical diagnosis of CML, classical banding
techniques, fluorescence in situ hybridization (FISH) probing for the Philadelphia chromosome (Ph) or polymerase chain
reaction amplifying the fusion products of the BCR-ABL fusion are state of the art techniques. Nevertheless, the genome
of CML patients harbors many more cytogenetic changes. These might be hidden in subpopulations due to clonal events
or involved in extremely complex aberrations. To identify these additional changes, several cytogenetic and molecular genetic
techniques could be applied. Nevertheless, it has been proposed that identifying these aberrations is time consuming
and costly and since they cannot be converted into a benefit for the patients, the necessity to perform these investigations
has been questioned. In the times where highly specialized medicine is advancing into several areas of cancer, this attitude
needs to be reassessed. Therefore, we looked at the usefulness of a combination of different techniques to unravel the genetic
changes in CML patients and to identify new chromosomal aberrations, which potentially can be correlated to different
stages of the disease and the strength of therapy resistance. We are convinced that the combination of these techniques
could be extremely useful in unraveling even the most complex karyotypes and in dissecting different clones contributing
to the disease. We propose that by doing so, this would improve CML diagnostic and prognostic findings, especially
with regard to CML resistance mechanisms and new therapeutic strategies.
