A New Valuable Tool in Monitoring Minimal Residual Disease for Patients with Acute Myeloid Leukemia

Circulating tumor DNA (ctDNA) is the soluble and tumor-derived DNA in plasma which carries the same mutations as the tumor cellular DNA. The aim of this study is to monitor minimal residual diseases (MRD) by IGH and TCR monoclonal gene rearrangement using ctDNA from AML patients without recurrent genetics abnormalities or other special karyotype abnormalities. Patients were diagnosed according to WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue (4^th edition). CtDNA, DNA extracted form bone marrow(BM's DNA) and DNA extracted from peripheral blood(PB's DNA) were obtained synchronously in 470 patients with AML (238male; 232female, with age ranging frome 14-60 years). DNAs were amplified by multiplex PCR and RQ-PCR. The DNA smaples from the patients were collected both at the initial diagnosis and in subsequent follow-up. In ctDNA, 178 cases showed monoclonal IGH rearrangement (37.87%) , while 164 revealed monoclonal TCR rearrangement (34.89%). Thirty-five patients had both IGH and TCR rearrangement simultaneously . No statistically significant difference was identified between ctDNA and BM's DNA with IGH (=1.32, P=0.25) and TCR (=0.45, P=0.5). After the first course of chemotherapy, 283 patients achieved completeremission. In 167 patients, IGH and TCR rearrangements were not detected in follow-up examinations from both ctDNA and BM's DNA. In 105 relapsed patinets, gene rearrangements became positive in both ctDNA and BM's DNA at the same time prior to the clinical relapse. For11 relapsed patients, the relative expression of IGH/TCR rearrangements/albumin in ctDNA had already exceeded the threshold value; while results in BM'DNA and PB'DNA were still negative, indicating that the change was detected earlier in ctDNA than that in BM cells (median, 31 days). In 11 patients diagnosed as extramedullary relapse, no statistically significant difference was identified in monitor MRD between ctDNA and BM's DNA (F=0.290, P=0.661). The clinical characteristics of the patients with differentgenotypes were compared. The median WBC, serum LDH level, the expression of CD7, CD19, CD56 , CD4, and DFS were statistically different for IGH^pos and TCR^pos genetype (P=0.010, 0.010, 0.024, 0.016, 0.010, 0.011, 0.016). In conclusion, for AML patients without special karyotype abnormalities, detecting IGH and TCR monoclonal rearrangement using ctDNA has the same clinical significance as BM's DNA in MRD evalaution. In addition, ctDNA could detect disease relapse earlier. Moreover, using ctDNA is more convenient and less invasive that can be used for a variety of clinical and research purposes.