title: T cell receptor genotyping and HOXA/TLX1 expression define three T lymphoblastic lymphoma subsets which might affect clinical outcome.
abstract: OBJECTIVE
  T lymphoblastic lymphomas (T-LBL) are rare disorders of immature T cells which predominantly involve the mediastinum. Their oncogenic pathways and prognostic variables are not clear.
  
  
  METHODS
  We undertook a retrospective study of 41 cytoplasmic CD3+ T-LBL (nine cases aged <16 years) by assessing stage of maturation arrest based on T cell receptor (TCR) immunogenotyping, immunohistochemistry, and quantification of the oncogenes thought to be important in immature T cell malignancies.
  
  
  RESULTS
  Application of a TCR-based immunogenetic classification allowed the identification of three subcategories: 11 immature IM0/D-LBL showed no TCR or only incomplete TCRD DJ rearrangement and corresponded to cytoplasmic CD3+ precursors of uncertain lineage. Sixteen mature TCRD(del)-LBL showed biallelic TCRD deletion and both TCRG and TCRB rearrangement, consistent with TCRalphabeta lineage restriction. Fourteen intermediate LBL (Int-LBL) showed complete TCRD VDJ and TCRG VJ rearrangement, with TCRB VDJ rearrangement in the majority. All Int-LBL expressed HOX11/TLX1 or HOXA9 transcripts and a proportion of the latter were associated with CALM-AF10 or NUP214-ABL fusion transcripts. IM0/D-LBL were restricted to adults with extrathymic disease and bone marrow involvement, whereas Int-LBL and TCRD(del)-LBL were found in children and adults with predominantly thymic disease. In adults, the Int-LBL subgroup was associated with a significantly superior clinical outcome. This subgroup can be identified either by TCR immunogenotyping or HOXA9/TLX1 transcript quantification.
  
  
  CONCLUSIONS
  Application of this molecular classification will allow the prospective evaluation of prognostic effects within pediatric and adult protocols.
authors.affiliation: INSERM EMI0210, and Université Paris V, Hopital Necker Enfants-Malades, Assistance Publique-Hopitaux de Paris (AP-HP), Paris, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Baleydier
authors.forename: Anne-Valerie
authors.initials: AV
authors.lastname: Decouvelaere
authors.forename: Julie
authors.initials: J
authors.lastname: Bergeron
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.forename: Stephane
authors.initials: S
authors.lastname: Lepretre
authors.forename: Barbara
authors.initials: B
authors.lastname: Petit
authors.forename: Herve
authors.initials: H
authors.lastname: Dombret
authors.forename: Kheira
authors.initials: K
authors.lastname: Beldjord
authors.forename: Thierry
authors.initials: T
authors.lastname: Molina
authors.forename: Vahid
authors.initials: V
authors.lastname: Asnafi
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macintyre
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000235:genetics; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051881:Receptor, Notch1 / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D011948:Receptors, Antigen, T-Cell; C071250:TLX1 protein, human; C088144:HoxA protein