Activation-induced cytidine deaminase expression in patients with myelodysplastic syndrome and its relationship with prognosis and treatment

Abstract

Background and Aim: Activation induced cytidine deaminase (AID) enables antibody diversity in B lymphocytes. It may also have an effect on MDS pathogenesis by causing somatic mutations and by inducing epigenetic changes in myeloid cells. This study aimed to compare AID expression of MDS patients with healthy controls, of MDS patients in different risk groups and of MDS patients according to their treatment.Materials and Methods: Total RNA was isolated and complementary DNA (cDNA) was transcribed from the peripheral blood samples of MDS patients and healthy controls. AID and the reference gene HPRT1 were analysed using Quantitative Real-time PCR(QRT-PCR). AID expression relative to HPRT1 was calculated. Patients were classified into "lower risk" and "higher risk" subgroups according to their initial IPSS and IPSS-R scores and their MDS subtypes at the time of study. Patients were also divided into two groups based on receiving treatment with hypomethylating agents. AID expression of different groups were compared using Mann-Whitney U test.Results: Thirty MDS patients and thirty healthy controls were included. AID expression in MDS patients was significantly higher compared to healthy controls (p<0.001). There was no significant difference in AID expression of "lower risk" and "higher risk" subgroups of patients. Patients that received hypomethylating agents did not have a significant difference in AID expression compared with patients that did not receive hypomethylating agents. Conclusion:AID expression is increased in the peripheral blood of MDS patients compared to healthy controls. However, AID expression is not significantly different in "lower risk" and "higher risk" subgroups and in patients treated with hypomethylating agents. Increased AID expression may be an early step in MDS pathogenesis.

Cytidine deaminase status as a marker of response to azacytidine treatment in MDS and AML patients

“…CDA activity was lower in AML patients compared to MDS patients, for which we have no explanation so far. We can hypothesise firstly a blastic clearance of CDA, secondly a role in the physiopathology of the disease with increased CDA expression in the peripheral blood of MDS patients compared to healthy controls 20 with more severe disease in deficient patients and thirdly a possible role of PNN in CDA synthesis. Here, in contrast to some previous clinical reports, no gender effect on CDA activities was found 21 .…”

Activation-Induced Cytidine Deaminase Expression in Patients with Chronic Myeloid Leukemia

“…Previous studies on myelodysplastic syndrome and myeloproliferative neoplasms have found a strong association between AID overexpression and these malignancies (14,17)…”

“…Numerous reports are found stating deregulated AID activity to be able to induce various types of cancer, mainly as a result of its overexpression (11)(12)(13)(14). This study aimed to identify the state of AID expression in CML patients and to reveal AID's etiopathogenic role, which is not yet fully understood.…”