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 th an 0.05% of pediatric acute lymphoblastic leukemia (ALL) patients. Thi s translocation encodes a TEL/AML-1 chimeric product comprising the he lix-loop-helix domain of TEL, a member of the ETS-like family of trans cription factors, fused to AML-1, the DNA-binding subunit of the AML-1 /CBF beta transcription factor complex. Both TEL and AML-1 are involve d 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 t he most common genetic lesion in these patients. Moreover, TEL/AML1 ex pression defined a distinct subgroup of patients characterized by an a ge between 1 and 10 years, B lineage immunophenotype, non-hyperdiploid DNA content and an excellent prognosis. These data demonstrate that m olecular diagnostic approaches are invaluable in identifying clinicall y distinct subgroups, and that the AML1/CBF beta transcription complex is the most frequent target of chromosomal rearrangements in human le ukemia.