부산대학교 도서관

Simple Summary: Acute Myeloid Leukemia is the most common leukemia in adults and has a dismal prognosis. An allogeneic bone marrow transplant provides the best curative approach. However, due to its related morbidity and mortality, the decision is based on risk assessment at diagnosis and response to therapy. Accurate assessment of molecular Minimal Residual Disease (MRD) has provided a powerful tool to assess the depth of response and risk of relapse. However, validated and standardized molecular MRD is currently limited to typical NPM1 mutations and core-binding factor translocations. To allow for a better standardization of other identified mutations, we constructed a vector that bears both the sequence for the mutation of interest and the ABL1 gene, thus allowing us to calculate the mutation copy number using the inherent ABL1 gene standards. We have implanted this approach in several identified mutations including atypical NPM1, IDH1/2 and RUNX1. Quantitative PCR for specific mutation is being increasingly used in Acute Myeloid Leukemia (AML) to assess Measurable Residual Disease (MRD), allowing for more tailored clinical decisions. To date, standardized molecular MRD is limited to typical NPM1 mutations and core binding factor translocations, with clear prognostic and clinical implications. The monitoring of other identified mutations lacks standardization, limiting its use and incorporation in clinical trials. To overcome this problem, we designed a plasmid bearing both the sequence of the mutation of interest and the ABL reference gene. This allows the use of commercial standards for ABL to determine the MRD response in copy number. We provide technical aspects of this approach as well as our experience with 19 patients with atypical NPM1, RUNX1 and IDH1/2 mutations. In all cases, we demonstrate a correlation between response and copy number. We further demonstrate how copy number monitoring can modulate the clinical management. Taken together, we provide proof of concept of a novel yet simple tool, which allows in-house MRD monitoring for identified mutations, with ABL-based commercial standards. This approach would facilitate large multi-center studies assessing the clinical relevance of selected MRD monitoring. [ABSTRACT FROM AUTHOR]