An NGS based MRD evaluation from acute myeloid leukemia patients

Abstract

Introduction: Measurable residual disease (MRD) is a prognostic factor for acute myeloid leukemia (AML). A next-generation sequencing (NGS) based MRD panel was developed and the results were validated. Methods:The NGS sequencing data was collected from 1003 Chinese AML patients. Results:The sequencing data from 586 newly diagnosed AML patients showed that NRAS mutation was most common (20.8%), followed by NPM1 (19.4%), FLT3-ITD (18.5%), and DNMT3A (15.4%). NPM1 and FLT3-ITD mutations were less in Chinese than in Caucasian AML patients, and the result of KRAS mutation was opposite. A new panel named "AML NGS-MRD hot-spot panel" was designed, containing 178 hot-spot exons from 52 mutated genes and only 62.8 Kb in size. With this hot-spot panel, 92.5% newly diagnosed AML patients were found to carry ≥1 mutations. To verify the performance of this panel, additional 205 newly diagnosed AML patients and 212 posttreatment AML patients were evaluated, and the hot-spot panel achieved a similar detection rate (91.2% for newly diagnosed AML patients and 89.2% for posttreatment AML patients). Finally, this study found that the mutation frequencies of signaling pathway genes (e.g., KRAS, NRAS, FLT3-ITD, KIT) were significantly reduced in post-treatment AML. Conclusion:The "AML NGS-MRD hot-spot panel" detected the mutations from relapsed AML patients with minimal panel size, and was a reliable and cost-effective panel for AML patients.

Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis

“…Therefore, inhibiting tumor angiogenesis and blocking the nutrient supply for angiogenesis has become a new opportunity for treatment[ 26 ]. Chen et al [ 27 ] showed that leukemia cells in patients with AML can autonomously secrete VEGF. After combining with VEGFR, the cells promote micro-angiogenesis and cell proliferation in the body, creating a pathway for leukemia cells to metastasize to other organs.…”

Acute Myeloid Leukemia and Next-Generation Sequencing Panels for Diagnosis: A Comprehensive Review

“…23 Panel should also exclude mutations consistent with premalignant clonal hematopoiesis (eg, DNMT3A, TET2, ASXL1). 68 Few studies conducted to study tailored post remission approach using MRD showed positive outcome, 69,70 but further information from prospective trials is still needed.…”