Architectural Clones in Aplastic Anaemia- Lessons Learned from High Throughput Sequencing.

Abstract

The use of targeted sequencing and unbiased whole exome sequencing has detected the presence of MDS-related mutations in nearly 20-25% of patients with bonafide AA, with mutations more commonly seen in epigenetic regulators such as DNMT3A, ASXL1 and BCOR. The implications of these mutations and their hierarchical order, especially in the context of predicting evolution to MDS, is still being explored and further data, especially with serial sampling at various time points during the course of the disease, are critically important. The understanding of the impact of replicative stress due to telomere attrition, and its interaction with clonal haemopoiesis of aging, acquisition of clonal abnormalities in the context of immune dysregulation and reduced stem cell numbers is still in its infancy.