Genomic analysis in myeloid sarcoma and comparison with paired acute myeloid leukemia

Hum Pathol. 2021 Feb:108:76-83. doi: 10.1016/j.humpath.2020.11.005. Epub 2020 Nov 21.

Abstract

Myeloid sarcoma (MS) is a rare manifestation of acute myeloid leukemia (AML) characterized by extramedullary proliferation of myeloid blasts. Owing to the rarity of MS, the clonal evolution of cell populations giving rise to MS is not well understood. To study the genomic signature of MS, we used a capture-based next-generation sequencing panel targeting 479 cancer genes to interrogate the genetic variants present in MS samples and compared their genetic profiles with their paired AML samples from a cohort of seven individuals. We identified a spectrum of single-nucleotide variants (SNVs) and a spectrum of copy number alterations in MS. Our study found that variant profiles observed in MS were generally similar to AML from the same individual, supporting the notion that these tumors are derived from a common precursor, rather than de novo tumors in a susceptible host. In addition, MS cases with a higher number of SNVs show worse clinical outcomes than MS with a lower number of SNVs. Identification of these abnormalities could potentially contribute to improved prognostic classification and identify new therapeutic targets for MS.

Keywords: Acute myeloid leukemia; Myeloid sarcoma; Next-generation sequencing; Single-nucleotide variants.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Copy Number Variations
  • Female
  • Gene Expression Profiling
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Sarcoma, Myeloid / genetics*
  • Transcriptome
  • Young Adult