Activation-Induced Cytidine Deaminase Transcripts Linked to More Aggressive CLL

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AID is a mutator enzyme that plays an essential role for somatic hypermutation and class switch recombination during effective adaptive immune responses.
AID is a mutator enzyme that plays an essential role for somatic hypermutation and class switch recombination during effective adaptive immune responses.

Researchers have identified an association between higher activation-induced cytidine deaminase (AID) transcript levels and trisomy of chromosome 12 and unmutated IGHV status in patients with chronic lymphocytic leukemia (CLL).1

According to the study, AID is a mutator enzyme that plays an essential role for somatic hypermutation and class switch recombination during effective adaptive immune responses. Previous research has shown that alternatively spliced AID variants have been documented in CLL.

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Here, researchers used real-time polymerase chain reaction (PCR) to quantify the expression of AID and its alternatively spliced transcripts in 149 patients with CLL. Patients were diagnosed between 1993 and 2014.

The researchers found 4 out of 5 AID variants to be frequently expressed among these patients. Only 13% of the samples expressed no AID variant. Seventy-five percent of cases expressed several AID variants, and almost half expressed all 4 AID transcripts.

There was also an association between higher AID transcript levels and trisomy of chromosome 12.

“CLL patients with trisomy 12 constitute a heterogeneous group with an intermediate prognosis,” the researchers wrote. “Trisomy 12 has been associated with mutations in the NOTCH1 gene as well as with Richter transformation, with both events being linked to aggressive disease and inferior clinical outcome.”

Functional analysis of AID splice variants showed loss of their activity with respect to somatic hypermutations, class switch recombination, and induction of double-strand DNA breaks.

Reference

  1. Zaprazna K, Reblova K, Svobodova V, et al. Activation-induced deaminase and its splice variants associate with trisomy 12 in chronic lymphocytic leukemia [published online October 27, 2018]. Ann Hematol. doi: 10.1007/s00277-018-3520-5

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