By Diagnostics World Staff
August 23, 2018 | This week, the Association for Molecular Pathology (AMP) published consensus, evidence-based recommendations to aid clinical laboratory professionals with the management of most Chronic Myeloid Neoplasms (CMNs) and development of high-throughput pan-myeloid sequencing testing panels.
The report, “Clinical Significance of DNA Variants in Chronic Myeloid Neoplasms (CMNs): A Report of the Association for Molecular Pathology,” was released online ahead of publication in The Journal of Molecular Diagnostics (DOI: 10.1016/j.jmoldx.2018.07.002).
CMNs are a complex group of hematopoietic disorders, encompassing myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), and the overlap entities (MDS/MPNs), that causes a person’s bone marrow to make too many, or too few, red blood cells, white blood cells or platelets. Next-generation sequencing (NGS) panels has enabled scientists to explore the genetic heterogeneity and clinical relevance of the small DNA variants in CMNs, but the biological complexity and multiple forms of CMNs has led to variability in the genes included on the available panels that are used to make an accurate diagnosis, provide reliable prognostic information, and select an appropriate therapy based on DNA variant profiles present at various time points.
The AMP CMN Working Group was established to review published literature, summarize key findings that support clinical utility and define a minimum set of critical gene inclusions for all high-throughput pan-myeloid sequencing testing panels.
The AMP CMN Working Group proposed the following 34 genes as a minimum recommended testing list: ASXL1, BCOR, BCORL1, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NF1, NPM1, NRAS, PHF6, PPM1D, PTPN11, RAD21, RUNX1, SETBP1, SF3B1, SMC3, SRSF2, STAG2, TET2, TP53, U2AF1, and ZRSR2.
The majority of genes commonly containing variants in CMNs may be classified into several key pathways that span the breadth of cellular functions, most significantly receptor kinase signaling transduction, transcription via transcription factors, epigenetic modification, and RNA splicing, the authors write in the paper.
“Activity through these key pathways, which are all critically implicated in CMNs, regulates cell cycle progression, apoptosis, and protein degradation,” they continue.
“The molecular pathology community has witnessed a recent explosion of scientific literature highlighting the clinical significance of small DNA variants in CMNs,” said Rebecca F. McClure, MD, Associate Professor, Health Sciences North and the Northern Ontario School of Medicine, AMP CMN Working Group Member and Co-lead Author in a statement. “AMP’s working group recognized a clear unmet need for evidence-based recommendations to assist in the development of the high-quality pan-myeloid gene panels that provide relevant diagnostic and prognostic information and enable monitoring of clonal architecture.”