Divergent clonal evolution of a common precursor to mantle cell lymphoma and classic Hodgkin lymphoma

Cold Spring Harb Mol Case Stud. 2019 Dec 13;5(6):a004259. doi: 10.1101/mcs.a004259. Print 2019 Dec.

Abstract

Clonal heterogeneity and evolution of mantle cell lymphoma (MCL) remain unclear despite the progress in our understanding of its biology. Here, we report a 71-yr-old male patient with an aggressive MCL and depict the clonal evolution from initial diagnosis of typical MCL to relapsed blastoid MCL. During the course of the disease, the patient was diagnosed with classic Hodgkin lymphoma (CHL) and received a CHL therapeutic regimen. Molecular analysis by next-generation sequencing of both MCL and CHL demonstrated clonally related CHL with characteristic immunophenotype and PDL1/2 gains. Moreover, our data illustrate the clonal heterogeneity and acquisition of additional genetic aberrations including a rare fusion of SEC22B-NOTCH2 in the process of clonal evolution. Evidence obtained from our comprehensive immunophenotypic and genetic studies indicates that MCL and CHL can originate from a common precursor by divergent clonal evolution, which may pose a therapeutic challenge.

Keywords: B-cell lymphoma; Hodgkin lymphoma.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B7-H1 Antigen / genetics
  • Cell Proliferation / genetics
  • Clonal Evolution / genetics
  • High-Throughput Nucleotide Sequencing
  • Hodgkin Disease / genetics
  • Hodgkin Disease / pathology
  • Humans
  • Lymphoma, Mantle-Cell / diagnosis*
  • Lymphoma, Mantle-Cell / genetics*
  • Lymphoma, Mantle-Cell / pathology
  • Male
  • R-SNARE Proteins / genetics
  • Receptor, Notch2 / genetics

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • NOTCH2 protein, human
  • R-SNARE Proteins
  • Receptor, Notch2
  • Sec22B protein, human