Mutated TET2 is responsible for initiation but not relapse in a tMDS/AML case

Therapy-related Myelodysplastic Syndrome/Acute Myeloid Leukemia (t-MDS/AML) is a serious complication for cancer patients undergoing chemotherapy or radiation treatment. Determining the mechanisms behind disease progression will help to design further treatment strategies. The objective of this study was to investigate the genetic basis during t-MDS/AML development. A male patient of follicular lymphoma developed t-MDS/AML upon multiple chemotherapies. With bone marrow transplantation, the patient reached remission for six months but relapsed and died of complication thereafter. We analyzed the somatic mutations, and observed dynamic change of mutation during the disease development. We identified the mutation in TET2 at the diagnosis but the same mutation diminished at the relapse stage, suggesting that the TET2 -mutated clone played important roles in initiation but was not in the relapse of t-MDS/AML. Our study shows that somatic mutations can be dynamically changed during t-MDS/AML development. This information is important in order to understand the genetic basis of the disease and to develop proper treatment for the disease.