Clinical, phenotypic and genetic similarities and disparities between post-transplant and classical Hodgkin lymphomas with respect to therapeutic targets

Expert Opin Ther Targets. 2009 Oct;13(10):1137-45. doi: 10.1517/14728220903196779.

Abstract

Objective: Post-transplant Hodgkin lymphoma (ptHL) is a rare but serious complication. We explored the clinical, phenotypic and genetic similarities and disparities between ptHL and classical Hodgkin lymphoma (cHL) in immunocompetent patients and sought proteins/pathways in ptHL that might have potential as therapeutic targets.

Research design and methods: Eight ptHL cases in solid organ recipients (mean patient age 36 years; mean duration between organ transplant and onset of ptHL 80 months) were phenotypically and genotypically analyzed and the results were compared with known phenotypic and molecular characteristics of cHL.

Results: All ptHL expressed CD15, CD30 and LMP-1 of EBV; the B-cell markers BOB-1, Oct2, CD79a and CD20 were more commonly expressed in ptHL versus cHL (100%, 86%, 50% and 38% in ptHL compared to 6%, 14%, 10% and 33% in cHL, respectively); all ptHL expressed phosphoinositide 3-kinase (PI3K) versus 81% of cHL; 2/6 (33%) ptHL displayed gains at 9p24 that were similar to cHL (32%). The JAK2 downstream pSTAT3 slightly predominated in ptHL versus cHL (60% versus 50%). Clonal immunoglobulin gene rearrangements were found in 2/4 cases.

Conclusions: ptHL and cHL are closely related, but not identical, neoplasms, with the primary differences being the strict association with EBV infection, persistent phenotypic B-cell signature and high expression of PI3K as well as the slightly CD4-depleted but TIA-1/Granzyme B-enriched cellular background composition in ptHL.

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD / genetics
  • Antineoplastic Agents / pharmacology*
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Hodgkin Disease / chemically induced*
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / genetics*
  • Humans
  • Immunosuppression Therapy / adverse effects*
  • Immunosuppressive Agents / adverse effects*
  • Kidney Transplantation
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Antigens, CD
  • Antineoplastic Agents
  • Immunosuppressive Agents