Erasmus TCRγδ LGL study

Background

TCRγδ+ large granular lymphocyte (LGL) leukemia is a relatively rare variant of mature T-LGL leukemia. Data obtained in our laboratory from archival material of TCRγδ+ T-LGL cases has revealed clear signs of antigen selection (phenotype, TCR CDR3 regions, other selection determinants) (Sandberg Y et al., Leukemia 2006;20(3):505-13). This points to a role for antigenic stimulation in the pathogenesis of this disease. Apart from that, hardly anything is known on the molecular aberrations that drive this lymphoproliferation. We are therefore planning a continuation of our initial studies to further unravel the (immuno)pathogenesis of this disease. Given its low incidence of this disease, such a TCRγδ LGL study should be performed in the frame of an ERIC collaboration.

Goals

  1. To collect (immuno)biological and clinical data on a large cohort of well-defined TCRγδ LGL cases
  2. To evaluate the role of antigenic stimulation in the pathogenesis of this disease via immunophenotypic and molecular analysis of TCR antigen receptors
  3. To establish the involvement of molecular aberrations in the leukemogenesis of this disease via SNP array, micro array / gene expression profiling

Participants

The study is open to ERIC members, who want to contribute cases of TCRγδ LGL leukemia / lymphoproliferation.

Approach

Members can contribute in various ways:

  1. submission of data (e.g. immunophenotypic data, data on TCR antigen receptor sequences)
  2. shipment of DNA and/or RNA to the coordinating laboratory for molecular analyses (TCR, array)
  3. shipment of cell samples to the coordinating laboratory for further flowcytometric and/or molecular analyses (TCR, array)

First phase

  • Collection of data on immunophenotype, TCR antigen receptors etc.
  • Collection of questionnaires on clinical features

Second phase (coordinating laboratory)

  • Completion of immunophenotyping on cell samples (selected cases)
  • Completion of TCR sequence analysis on MNC gDNA (selected cases)

Third phase (coordinating laboratory)

  • SNP array analysis on gDNA, preferably from sorted leukemic cell population
  • Micro array analysis on RNA, from highly purified leukemic cell population

Time-line

Start: Mid 2011

Coordination

Anton W. Langerak, PhD
Rotterdam, The Netherlands
E-mail: