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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.
MedLine Citation:
PMID:  16956820     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVES: 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. DESIGN AND 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. INTERPRETATION AND 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:
Martine van Grotel; Jules P P Meijerink; H Berna Beverloo; Anton W Langerak; Jessica G C A M Buys-Gladdines; Pauline Schneider; Tim S Poulsen; Monique L den Boer; Martin Horstmann; Willem A Kamps; Anjo J P Veerman; Elisabeth R van Wering; Max M van Noesel; Rob Pieters
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Haematologica     Volume:  91     ISSN:  1592-8721     ISO Abbreviation:  Haematologica     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-07     Completed Date:  2006-10-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  1212-21     Citation Subset:  IM    
Affiliation:
Department of Pediatric Oncology/Hematology, room Sp2456, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, the Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Child
Child, Preschool
Chromosome Aberrations*
Cytogenetic Analysis*
Female
Humans
Leukemia-Lymphoma, Adult T-Cell / diagnosis*,  drug therapy
Male
Oncogene Proteins, Fusion
Prognosis
Retrospective Studies
Treatment Outcome
Chemical
Reg. No./Substance:
0/AF10-CALM fusion protein, human; 0/Oncogene Proteins, Fusion
Comments/Corrections
Comment In:
Haematologica. 2006 Sep;91(9):1156A   [PMID:  16956809 ]

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