Evaluation of minimal residual disease in acute myeloid leukemia with NPM1 marker

Background: minimal residual disease (mrd) tests provide early identification of hematologic relapse and timely management of acute myeloid leukemia (aml) patients. approximately,50% of aml patients do not have clonal chromosomal aberrations and categorize as a cytogenetically normal acute myeloid leukemia (cn-aml). about 60% of adult cn-aml has a mutation in exon 12 of npm1 gene. this mutation is specific for malignant clone and potentially is a good marker of mrd. in this retrospective study,we set up a quantitative test for quantifying npm1 type a mutation and aml patients carrying this mutation at the time of diagnosis,were followed-up. materials and methods: we prepared plasmids containing a cdna fragment of npm1 and abl genes by pcr cloning. the plasmids were used to construct standard curves. eleven patients were analyzed using established method. serial pb and/or bm samples (n=71) were taken in 1-3 months intervals (mean 1.5-month intervals) and median follow-up duration after chemotherapy was 11 months (5-28.5 months). results: in this study,we developed rna-based rq-pcr to quantitation of npm1 mutation a with sensitivities of 10(-5). the percent of npmmut/abl level showed a range between 132 and 757 with median of 383.5 in samples at diagnosis. the median npmmut transcript level log reduction was 3 logs. relapse occurred in 54.5% of patients (n=6),all cases at diagnosis demonstrated the same mutation at relapse. in patients who experienced relapse,log reduction levels of npm1 mrna transcript after therapy were 4 (n=2),3 (n=2) and 1 log (n=2). totally,npmmut level showed less than 5 log reduction in all of them,whereas this reduction was 5-6 logs in other patients. conclusion: despite the limitations of this study in terms of sample size and duration of follow-up,it showed the accuracy of set up for detection of mutation and this marker has worth for following-up at different stages of disease. because of high frequency,stability,specificity to abnormal clone and high sensitivity,npm1 is a suitable marker for monitoring of npmc+ aml patients. © 2016,tehran university of medical sciences (tums). all rights reserved.