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Role of ERG Amplification in AML Oncogenesis

By: Lauren Harrison, MS
Posted: Tuesday, March 22, 2022

Copy number amplification of the ETS-related gene (ERG), a member of the ETS family of transcription factors located on chromosome 21q22.2, is a recurrent secondary event in acute myeloid leukemia (AML), according to research published in Genes Chromosomes & Cancer by Lina Shao, MD, PhD, and colleagues at the University of Michigan in Ann Arbor.

A total of 14 cases of AML with ERG amplification were retrospectively identified by copy number microarray. The amplifications occur as variably sized segments with allelic imbalances. Metaphase and interphase fluorescent in situ hybridization studies using break-apart probes flanking ERG demonstrate three patterns of amplification: intrachromosomal amplification, double minute chromosomes (without centromeres), and increased marker chromosomes (with centromeres). These amplifications are associated with complex karyotype and TP53 alterations. Low-level subclonal ERG amplification was identified in two cases of de novo myelodysplastic syndrome, supporting the notion that ERG amplification arises as a secondary event. There is no conclusive evidence to suggest ERG amplification leads to increased ERG protein levels.

Of interest, the case of AML with the highest expression of the ERG protein also had the highest level of ERG amplification. In this small cohort of AML with a complex karyotype, the presence of ERG amplification did not significantly impact overall survival.

Disclosure: The study authors reported no conflicts of interest.


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