The contribution of MYC and PLK1 expression to proliferative capacity in diffuse large B-cell lymphoma

Leuk Lymphoma. 2019 Dec;60(13):3214-3224. doi: 10.1080/10428194.2019.1633629. Epub 2019 Jul 1.

Abstract

Polo-like kinase-1 (PLK1) regulates the MYC-dependent kinome in aggressive B-cell lymphoma. However, the role of PLK1 and MYC toward proliferation in diffuse large B-cell lymphoma (DLBCL) is unknown. We use multiplexed fluorescent immunohistochemistry (fIHC) to evaluate the co-localization of MYC, PLK1 and Ki67 to study their association with proliferation in DLBCL. The majority (98%, 95% CI 95-100%) of MYC/PLK1-double positive tumor cells expressed Ki67, underscoring the key role of the MYC/PLK1 circuit in proliferation. However, only 38% (95% CI 23-40%) and 51% (95% CI 46-51%) of Ki67-positive cells expressed MYC and PLK1, respectively. Notably, 40% (95% CI 26-43%) of Ki67-positive cells are MYC- and PLK-negative. A stronger correlation exists between PLK1 and Ki67 expression (R = 0.74, p < .001) than with MYC and Ki67 expression (R = 0.52, p < .001). Overall, the results indicate that PLK1 has a higher association than MYC in DLBCL proliferation and there are mechanisms besides MYC and PLK1 influencing DLBCL proliferation.

Keywords: Diffuse large B cell lymphoma; Ki67; MYC; PLK1; fluorescence immunohistochemistry; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / metabolism*
  • Cell Proliferation*
  • Humans
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / analysis
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-myc / analysis
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Software

Substances

  • Cell Cycle Proteins
  • Ki-67 Antigen
  • MKI67 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Protein Serine-Threonine Kinases