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.
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.
van Grotel
Martine
M
Department of Pediatric Oncology/Hematology, room Sp2456, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, the Netherlands.
Meijerink
Jules P P
JP
Beverloo
H Berna
HB
Langerak
Anton W
AW
Buys-Gladdines
Jessica G C A M
JG
Schneider
Pauline
P
Poulsen
Tim S
TS
den Boer
Monique L
ML
Horstmann
Martin
M
Kamps
Willem A
WA
Veerman
Anjo J P
AJ
van Wering
Elisabeth R
ER
van Noesel
Max M
MM
Pieters
Rob
R
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
C114359:AF10-CALM fusion protein, human; D015514:Oncogene Proteins, Fusion