Array CGH in Human Leukemia: From Somatics to Genetics

Abstract

During the past decade, array CGH has been applied to study copy number alterations in the genome in human leukemia in relation to prediction of prognosis or responsiveness to therapy. In the first segment of this review, we will focus on the identification of acquired mutations by array CGH, followed by studies on the pathogenesis of leukemia associated with germline genetic variants, phenotypic presentation and response to treatment. In the last section, we will discuss constitutional genomic aberrations causally related to myeloid leukemogenesis.

On the Power of Additional and Complex Chromosomal Aberrations in CML

“…Furthermore, invariant aberrations can be used as clonal markers to detect and follow minimal residual disease and relapse [19]. …”

“…This finding is of great interest especially in view of the increasing number of published data on this subject and their prognostic implications [35]. Nevertheless, many of these drawbacks connected to classical CGH have been overcome by the array CGH technology [19]. …”

“…Here, additionally to classical cytogenetic analysis [13] samples could be systematically investigated by fluorescence in situ hybridization (FISH, [14]), multicolor fluorescence in situ hybridization (M-FISH, [15]), classical comparative genomic hybridization (CGH [16-18] or array CGH [19]). The aim of applying the different cytogenetic methods would be to get maximum information on the karyotypic changes present in each case and at the different stages of the disease.…”

“…The CGH technique has been described as the method-of-choice for detecting tumor genome imbalances, like copy number gain or losses, especially when archival, non-proliferating specimens are analyzed. Results have been reported for example for lymphomas and leukemias [20-23] and for example for myeloid leukemogenesis applying array CGH [19]. Nevertheless, only few reports describing the application of CGH in CML research have been published [24-26].…”

“…Additionally, sub-chromosomal aberrations might be visualized or overlooked by CGH depending on the percentage of total cells that certain clones have. Quite contrary, array CGH with it’s much higher resolution would allow to detect these smaller changes as well [19]. …”