TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis.
The t(12;21)(p13;q22) is identified by routine cytogenetics in less than 0.05% of pediatric acute lymphoblastic leukemia (ALL) patients. This translocation encodes a TEL/AML-1 chimeric product comprising the helix-loop-helix domain of TEL, a member of the ETS-like family of transcription factors, fused to AML-1, the DNA-binding subunit of the AML-1/CBF beta transcription factor complex. Both TEL and AML-1 are involved in several myeloid leukemia-associated translocations with AML-1/CBF beta being altered in 20-30% of de novo acute myeloid leukemia (AML) cases. We now demonstrate that a TEL/AML1 chimeric transcript encoded by a cryptic t(12;21) is observed in 22% of pediatric ALL, making it the most common genetic lesion in these patients. Moreover, TEL/AML1 expression defined a distinct subgroup of patients characterized by an age between 1 and 10 years, B lineage immunophenotype, non-hyperdiploid DNA content and an excellent prognosis. These data demonstrate that molecular diagnostic approaches are invaluable in identifying clinically distinct subgroups, and that the AML1/CBF beta transcription complex is the most frequent target of chromosomal rearrangements in human leukemia.
Shurtleff
S A
SA
Department of Pathology and Laboratory Medicine, St Jude Children's Research Hospital, Memphis, TN, USA.
Buijs
A
A
Behm
F G
FG
Rubnitz
J E
JE
Raimondi
S C
SC
Hancock
M L
ML
Chan
G C
GC
Pui
C H
CH
Grosveld
G
G
Downing
J R
JR
D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C493728:RUNX1 protein, human