THE COMMON TEL AML1 REARRANGEMENT DOES NOT REPRESENT A FREQUENT EVENTIN ACUTE LYMPHOBLASTIC-LEUKEMIA OCCURRING IN CHILDREN WITH DOWN-SYNDROME/

Individuals with constitutional trisomy 21 (Down syndrome) are at incr eased risk of developing acute leukaemias, both of myeloid and lymphoi d lineage. Although the cause of leukaemia in Down syndrome (DS) remai ns unknown, potential candidate genes include the ones on chromosome 2 1, and in particular AML1, the rearrangement of which in the t(8,21) i s associated with the French-American-British (FAB) classification M2 subtype of acute myeloid leukaemia (AML) in the general population and has been described in Down patients with AML-M2. Recently, a new rear rangement involving AML1, the t(12;21), producing the TEL/AML1 hybrid transcript, has bean described by molecular analysis as the most recur rent genetic lesion in childhood acute lymphoblastic leukemia (ALL). I n order to investigate whether the t(12;21) could give a molecular clu e as to the precise basis of the etiologic association between DS and acute lymphoblastic leukemia, we tested a series of 11 consecutive cas es af ALL in DS children for the presence of the TEL/AML1 transcript, by RT-PGR analysis. We report absence of the TEL/AML1 rearrangement am ong the 11 cases tested. This data may be suggestive of alternative pa thways involved in the pathogenesis of ALL in children with constituti onal trisomy 21.