TEL-AML1 FUSION RNA AS A NEW TARGET TO DETECT MINIMAL RESIDUAL DISEASE IN PEDIATRIC B-CELL PRECURSOR ACUTE LYMPHOBLASTIC-LEUKEMIA

It has recently been shown that the t(12;21)(p13;q22) translocation fu ses two genes, TEL on chromosome 12 and AML1 on chromosome 21. We have evaluated the frequency of this newly described translocation in acut e lymphoblastic leukemia (ALL), and the feasibility of minimal residua l disease (MRD) monitoring by polymerase chain reaction (PCR) amplific ation of TEL-AML1 transcripts. Thirty-nine adult- and 45 childhood-ALL s consecutively diagnosed in a single center were included in this stu dy. TEL-AML1 fusion transcripts were searched for in the 39 adult- and 45 childhood-ALLs for which material was available. BCR-ABL, E2A-PBX1 , and MLL-AF4 transcripts were also studied by PCR in these cases. TEL -AML1 transcripts were found in 8 out of 35 (23%) childhood B-cell pre cursor ALLs (BCP-ALLs). TEL-AML1 transcripts were detected in only 1 o f 31 adult BCP-ALLs (P = .04, Fisher's exact test). Nevertheless, in t his adult case, TEL-AML1 transcripts were found at a low level in 2 of 3 different samples. BCR-ABL, E2A-PBX1, and MLL-AF4 transcripts were found in 12, 3, and 1 cases of 31 adult BCP-ALLs, and in 1, 2, and 1 c ases of 35 childhood BCP-ALLs, respectively. TEL-AML 1 transcripts wer e never found associated with any other fusion transcripts. Taken toge ther, the four types of chimeric transcripts were detected in 12 of 35 (34%) childhood BCP-ALL cases. No TEL-AML1 transcripts were detected in 11 T-cell ALLs (4 adults and 5 children), nor in 2 B-cell (slg+) AL Ls. MRD was evaluated in 21 samples collected in 9 TEL-AML1(+) childho od BCP-ALL cases during therapy (median follow-up = 200 days). Of 8 pa tients evaluated after induction therapy, 4 showed detectable but low levels of MRD. Of 7 patients serially evaluated, only one showed persi stence of detectable MRD. This study shows that TEL-AML1 transcripts a re frequently detected in pediatric BCP-ALLs and that these transcript s are molecular targets that will simplify the strategy of MRD monitor ing in childhood BCP-ALL. (C) 1996 by The American Society of Hematolo gy.