Clinical Significance of DNA Variants in Chronic Myeloid Neoplasms: A Report of the Association for Molecular Pathology

J Mol Diagn. 2018 Nov;20(6):717-737. doi: 10.1016/j.jmoldx.2018.07.002. Epub 2018 Aug 20.


To address the clinical relevance of small DNA variants in chronic myeloid neoplasms (CMNs), an Association for Molecular Pathology Working Group comprehensively reviewed published literature, summarized key findings that support clinical utility, and defined critical gene inclusions for high-throughput sequencing testing panels. This review highlights the biological complexity of CMNs [including myelodysplastic syndromes, myeloproliferative neoplasms, entities with overlapping features (myelodysplastic syndromes/myeloproliferative neoplasms), and systemic mastocytosis], the genetic heterogeneity within diagnostic categories, and similarities between apparently disparate diagnostic entities. The founding variant's hematopoietic differentiation compartment, specific genes and variants present, order of variant appearance, individual subclone dynamics, and therapeutic intervention all contribute to the clinicopathologic features of CMNs. Selection and efficacy of targeted therapies are increasingly based on DNA variant profiles present at various time points; therefore, high-throughput sequencing remains critical for patient management. The following genes are a minimum recommended list to provide relevant clinical information for the management of most CMNs: 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. This list is not comprehensive for all myeloid neoplasms and will evolve as insights into effects of combinations of relevant biomarkers on specific clinicopathologic characteristics of CMNs accumulate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Clone Cells
  • DNA, Neoplasm / genetics*
  • Disease Progression
  • Epigenesis, Genetic
  • Hematopoiesis / genetics
  • Histones / metabolism
  • Humans
  • Mutation / genetics*
  • Myeloproliferative Disorders / genetics*
  • Nucleophosmin
  • Pathology, Molecular*
  • Spliceosomes / metabolism
  • World Health Organization


  • DNA, Neoplasm
  • Histones
  • NPM1 protein, human
  • Nucleophosmin