The Association for Molecular Pathology (AMP) has recently published a report providing consensus, evidence-based recommendationsto aid clinical laboratory professionals with the management of most chronic myeloid neoplasms (CMNs) and development of pan-myeloid high-throughput sequencing panels.1
Rebecca F. McClure, MD, Northern Ontario School of Medicine.
CMNs are a complex group of hematopoietic disorders encompassing myelodysplastic syndromes (MDSs), myeloproliferative neoplasms (MPNs), and overlap entities (MDS/MPNs) that cause a person’s bone marrow to make too many, or too few, red blood cells, white blood cells. or platelets.
The increasing availability of targeted next-generation sequencing (NGS) panels has enabled scientists to explore the genetic heterogeneity and clinical relevance of the small DNA variants in CMNs. However, the biological complexity and multiple forms of CMNs have led to variability in the genes included on the test 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 pan-myeloid NGS testing panels.
“The molecular pathology community has witnessed a recent explosion of scientific literature highlighting the clinical significance of small DNA variants in CMNs,” says Rebecca F. McClure, MD, associate professor at the Northern Ontario School of Medicine and co-lead author of the report. “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.”
Annette Kim, MD, PhD, Harvard Medical School.
The working group proposed 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 list of genes is meant to aid clinical laboratory professionals with the management of most CMNs and selection of myeloid testing panels.
“While the goal of the study was to distill the literature for molecular pathologists, in doing so we also revealed recurrent mutational patterns of clonal evolution that will aid hematologist/oncologists, researchers, and pathologists understand how to interpret the results of these panels as they reveal critical biology of the neoplasms,” says Annette S. Kim, MD, PhD, associate professor of pathology at Harvard Medical School and chair of the CMN working group.
Mark D. Ewalt, MD, University of Colorado.
“This new CMN report is another validation of AMP’s commitment to continuously improve clinical practice and patient care,” says Mark D. Ewalt, MD, assistant professor of pathology atthe University of Colorado and co-lead author of the report. “Moving forward, the AMP CMN working group will plan on revisiting and updating the gene list as insight on specific clinicopathologic characteristics of CMNs accumulates.”
For additional information, visit the Association for Molecular Pathology.
Reference
- McClure RF, Ewalt MD, Crow J, et al. Clinical significance of DNA variants in chronic myeloid neoplasms (CMNs): a report of the Association for Molecular Pathology. J Mol Diagn. Epub ahead of print August 20, 2018; doi: 10.1016/j.jmoldx.2018.07.002.
