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

• Published in: Haematologica (Roma) 2006-09, Vol.91 (9), p.1212-1221
• Main Authors: van Grotel, M, Meijerink, JP, Beverloo, HB, Langerak, AW, Buys-Gladdines, JG, Schneider, P, Poulsen, TS, den Boer, ML, Horstmann, M, Kamps, WA, Veerman, AJ, van Wering, ER, van Noesel, MM, Pieters, R
• Format: Article
• Language: English
• Subjects: Adolescent; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Child; Child, Preschool; Chromosome Aberrations; Cytogenetic Analysis; Female; Humans; Leukemia-Lymphoma, Adult T-Cell - diagnosis; Leukemia-Lymphoma, Adult T-Cell - drug therapy; Male; Oncogene Proteins, Fusion; Prognosis; Retrospective Studies; Treatment Outcome
• ISSN: 0390-6078; 1592-8721

Department of Pediatric Oncology/Hematology, room Sp2456, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, the Netherlands. 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.