High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia

Abstract

The recurrent t(12;21)(p12;q22) translocation fuses two genes, TEL and AML1, that have previously been shown to be independently involved in myeloid malignant proliferations. A search for rearrangement of the TEL locus in the region known to be involved in t(12;21) was performed by Southern blotting in a panel of hematopoietic malignancies. The presence of a t(12;21) was confirmed by fluorescence in situ hybridization (FISH) and/or reverse transcriptase (RT)-polymerase chain reaction (PCR). We report that fusion of TEL to AML1 is specifically observed in at least 16% of the childhood B-lineage acute lymphoblastic leukemia (ALL) investigated, none of which had been previously identified as harboring t(12;21).

Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukaemia: a UK Cancer Cytogenetics Group Study

“…Thus, interphase FISH (iFISH) became the method of choice for detection of the high-risk chromosomal changes in UK ALL trials. The translocation, t(12;21)(p13;q22), giving rise to the TEL/AML1 (ETV6/RUNX1) fusion gene is found in c. 25% of childhood B-lineage ALL (Romana et al, 1995). As this translocation is not detectable by cytogenetic analysis (Romana et al, 1994), it seemed appropriate to include iFISH screening for this widespread fusion gene.…”

Outcome and lineage involvement in t(12;21) childhood acute lymphoblastic leukaemia

“…1 mg of RNA was reverse transcribed into cDNA by incubation at 42ЊC for 45 min with 50 U Moloney murine leukaemia virus reverse transcriptase (RT) and random examer primers (Perkin-Elmer, Norwalk, Ct., U.S.A.) followed by RT denaturation at 99ЊC for 5 min. For PCR amplification we used the conditions and oligonucleotide primers described by Romana et al (1995b). Adopting the previous PCR conditions, and adding the TEL sense 5 0 oligonucleotide (5'-CGTGGATTTCAAACAGTCCA-3 0 ) and 3 0 TEL antisense oligonucleotide (TEL antisense: 5 0 -GGCTCTGGACATTTTCTCAT-3 0 ), the expression of TEL gene was tested and used as the control for the RT-PCR.…”

“…The t(12;21)(p13;q22) translocation has been described recently as the most frequent genetic lesion of childhood ALLs. Although almost undetectable at the cytogenetic level, it has been reported to occur in 16-36% of childhood ALL series when tested by molecular techniques (Romana et al, 1995b;Shurtleff et al, 1995). The t(12;21), by fusing the TEL gene on chromosome 12p (Golub et al, 1994) to the AML1 gene on chromosome 21q , produces two hybrid transcripts, TEL/AML1 and AML1/TEL, the former being more consistently expressed in rearranged cases.…”

“…The t(12;21), by fusing the TEL gene on chromosome 12p (Golub et al, 1994) to the AML1 gene on chromosome 21q , produces two hybrid transcripts, TEL/AML1 and AML1/TEL, the former being more consistently expressed in rearranged cases. This translocation has been associated with B-precursor lineage involvement and it has been suggested that the TEL/AML1 transcript expression, though playing a leukaemogenic role, may identify a subset of ALL patients with excellent prognosis (Romana et al, 1995b;Shurtleff et al, 1995).…”

Quantification of TEL–AML1 transcript for minimal residual disease assessment in childhood acute lymphoblastic leukaemia

“…Although fusion transcripts are present only in 40% of childhood ALL, quantification of chimaeric messengers provides a useful alternative approach for MRD assessment because of its good sensitivity and because of the stability of such markers over time. The TEL±AML1 transcript, which is associated with t(12;21), is particularly interesting because it is found in 25% of childhood B-cell precursor ALL (Romana et al, 1995;Shurtleff et al, 1995;Raynaud et al, 1996;Borkhardt et al, 1997).…”