title: The outcome of molecular-cytogenetic subgroups in pediatric T-cell acute lymphoblastic leukemia: a retrospective study of patients treated according to DCOG or COALL protocols.
abstract: OBJECTIVE
  Subgroups of T-cell acute lymphoblastic leukemia (T-ALL), defined according to recurrent cytogenetic aberrations, may have different prognoses. The aim of this study was to determine the prognostic relevance of molecular-cytogenetic abnormalities in pediatric patients using quantitative real-time polymerase chain reaction and fluorescence in situ hybridization.
  
  
  METHODS
  The patients were assigned to TAL1, HOX11/TLX1, HOX11L2/TLX3, or CALM-AF10 subgroups. The cytogenetic subgroups were characterized in relation to immunophenotype and the expression of aberrantly expressed transcription factors.
  
  
  RESULTS
  In our cohort study, CALM-AF10 was associated with an immature immunophenotype and poor outcome (p=0.005). HOX11L2 was associated with both immunophenotypically immature cases as well as cases committed to the gammadelta-lineage. HOX11L2 was significantly associated with poor outcome (p=0.01), independently of the expression of CD1 or the presence of NOTCH1 mutations. TAL1 abnormalities were associated with alphabeta-lineage commitment, and tended to be associated with a good outcome. Cells in HOX11 cases resembled early CD1-positive cortical thymocytes without expression of Cytbeta and TCR molecules. In relation to the expression of early T-cell transcription factors, high TAL1 levels were found in immunophenotypically-advanced cases, whereas high LYL1 levels were found in immature subgroups.
  
  
  CONCLUSIONS
  The reported outcomes for HOX11L2-rearranged T-ALL cases are conflicting; the prognostic impact may depend on the therapy given. In our cohort, this cytogenetic aberration was associated with a poor outcome. Our data on CALM-AF10 rearranged T-ALL, albeit based on only three patients, suggest that this type of leukemia is associated with a poor outcome.
authors.affiliation: Department of Pediatric Oncology/Hematology, room Sp2456, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Martine
authors.initials: M
authors.lastname: van Grotel
authors.forename: Jules P P
authors.initials: JP
authors.lastname: Meijerink
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Jessica G C A M
authors.initials: JG
authors.lastname: Buys-Gladdines
authors.forename: Pauline
authors.initials: P
authors.lastname: Schneider
authors.forename: Tim S
authors.initials: TS
authors.lastname: Poulsen
authors.forename: Monique L
authors.initials: ML
authors.lastname: den Boer
authors.forename: Martin
authors.initials: M
authors.lastname: Horstmann
authors.forename: Willem A
authors.initials: WA
authors.lastname: Kamps
authors.forename: Anjo J P
authors.initials: AJ
authors.lastname: Veerman
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: van Wering
authors.forename: Max M
authors.initials: MM
authors.lastname: van Noesel
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis* / Q000188:drug therapy; D008297:Male; D015514:Oncogene Proteins, Fusion; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: C114359:AF10-CALM fusion protein, human; D015514:Oncogene Proteins, Fusion