Childhood acute lymphoblastic leukemia with the MLL-ENL fusion and t(11;19)(q23;p13.3) translocation.
OBJECTIVE
To determine the molecular characteristics, clinical features, and treatment outcomes of children with acute lymphoblastic leukemia (ALL) and the t(11;19)(q23,p13.3) translocation.


METHODS
A retrospective analysis of leukemic cell karyotypes obtained from patients with new diagnoses of ALL who were treated at St. Jude Children's Research Hospital or by the Pediatric Oncology Group was performed to identify cases with the t(11;19)(q23;p13.3) translocation. Molecular analyses were performed on these cases to determine the status of the MLL gene and the presence of the MLL-ENL fusion transcript.


RESULTS
Among 3,578 patients with ALL and successful cytogenetic analysis, we identified 35 patients with the t(11;19)(q23;p13.3) translocation: 13 infants and 11 older children had B-precursor leukemia, whereas 11 patients had a T-cell phenotype. Although all of the cases examined had MLL rearrangements and MLL-ENL fusion transcripts, outcome varied according to age and immunophenotype. Among B-precursor cases, only two of the 13 infants remain in complete remission, compared with six of the 11 older children. Most strikingly, no relapses have occurred among B-precursor patients 1 to 9 years of age or among T-cell patients.


CONCLUSIONS
Although MLL gene rearrangements are generally associated with a dismal outcome in ALL, two distinct subsets with MLL-ENL fusions have an excellent prognosis. Our results suggest that patients with this genetic abnormality who have T-cell ALL or are 1 to 9 years of age should not be considered candidates for hematopoietic stem-cell transplantation during their first remission.
Rubnitz
J E
JE
Department of Hematology/Oncology, St. Jude Children's Research Hospital, the University of Tennessee College of Medicine, Memphis 38105-2794, USA. jeffrey.rubnitz@stjude.org
Camitta
B M
BM
Mahmoud
H
H
Raimondi
S C
SC
Carroll
A J
AJ
Borowitz
M J
MJ
Shuster
J J
JJ
Link
M P
MP
Pullen
D J
DJ
Downing
J R
JR
Behm
F G
FG
Pui
C H
CH
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007621:Karyotyping; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D011379:Prognosis; D011519:Proto-Oncogenes; D012189:Retrospective Studies; D014157:Transcription Factors; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C081448:MLLT1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase