TEL-AML1 translocations with TEL and CDKN2 inactivation in acute lymphoblastic leukemia cell lines

Kim, Do-Hyung; Moldwin, Richard L.; Vignon, Christine; Bohlander, SK; Giordano, Lisa; Gupta, Rikisha; Fears, Scott C.; Nucifora, Giuseppina; Rowley, JD

doi:10.1182/blood.v88.3.785.bloodjournal883785

Cited by 11 publications

(27 citation statements)

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“…These results indicate that the second ETV6 allele was expressed and suggest that complete inactivation of this gene is not necessary for the leukaemic transformation of cells with the t(12;21). A recent report on ETV6 analysis in leukaemic cell lines indicates that in two patients (one with a t(12;21) and one without t(12;21)), normal ETV6 mRNA was present in the early-stage cell lines, whereas it was not expressed in the cell lines established from the same patients in late-stage disease (Kim et al, 1996). These data support the idea that complete inactivation of ETV6 contributes to tumour progression.…”

Section: Discussionsupporting

confidence: 64%

Analysis of ETV6 and ETV6‐AML1 proteins in acute lymphoblastic leukaemia

Agapé

Gérard

Cavé³

et al. 1997

Br J Haematol

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Summary. The t(12;21) is a recurring chromosomal abnormality in acute lymphoblastic leukaemias (ALLs) which results in the production of an ETV6-AML1 fusion gene. The association between t(12;21) and the deletion of the untranslocated allele of ETV6 is among the most frequent abnormalities observed in B-lineage ALLs in children. In order to study the proteins encoded by ETV6 and ETV6-AML1, we raised polyclonal antibodies directed against a recombinant peptide corresponding to the junctional region of ETV6-AML1. Cell lysates from various leukaemic cell lines, and from children with B-and T-lineage ALLs, were studied by Western blot.Two isoforms of ETV6 protein were detected in normal bone marrow cells and in leukaemic cells without 12p alteration: a major form (apparent m.w. 63 kD) and a minor one (apparent m.w. 53 kD).In the REH cell line, which expresses the ETV6-AML1 fusion transcript and no normal ETV6 mRNA, the ETV6 isoforms were absent and two new bands were detected corresponding to ETV6-AML1 protein products (apparent m.w. 95 and 105 kD). A similar pattern was obtained with blast cells from patients with a t(12;21) and a deletion of ETV6.In two patients with a t(12;21) but no deletion of ETV6, four bands were detected corresponding to both the normal ETV6 and ETV6-AML1 proteins, suggesting that in these cases the second ETV6 allele was not inactivated.Surprisingly, the expression pattern of ETV6 differed widely from patient to patient. In three out of 13 patients without t(12;21), the relative intensity of the bands corresponding to ETV6 isoforms in blast cells from patients was completely different from normal cells, with a marked predominance of the 53 kD isoform. The pattern of ETV6 expression was normal in bone marrow from the same patients during remission. These finding suggest that ETV6 abnormalities are not restricted to patients with translocations or deletions involving this gene.

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Section: Discussionsupporting

confidence: 64%

Analysis of ETV6 and ETV6‐AML1 proteins in acute lymphoblastic leukaemia

Agapé

Gérard

Cavé³

et al. 1997

Br J Haematol

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“…RT-PCR analysis. Total RNA was isolated from frozen blood cells using a Purescript kit (Gentra Systems Inc., U.S.A.) according to the manufacturer's instructions, and TEL-AML1 fusion transcripts were detected by RT-PCR as described by Kim et al (1996).…”

Section: Methodsmentioning

confidence: 99%

An investigation of the t(12;21) rearrangement in children with B‐precursor acute lymphoblastic leukaemia using cytogenetic and molecular methods

Kempski¹,

Chalker²,

Chessells

et al. 1999

Br J Haematol

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Summary. The t(12;21) is the commonest recurrent translocation in childhood acute lymphoblastic leukaemia (ALL), the presence of which has been suggested to be a good prognostic feature. We have studied 22 childhood cases of B-precursor ALL with this rearrangement, and have found no significant differences in event-free survival between these and a control group of patients with similar phenotypes. Using a variety of cytogenetic and molecular techniques, we have confirmed a strong association with co-expression of myeloid markers, frequent deletions of the short-arm of the untranslocated chromosome 12 homologue and duplication of the derivative chromosome 21. Intragenic deletion of the untranslocated ETV6 gene in 3/12 informative patients points to the likelihood of this gene being a target for deletion.

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“…[21][22][23] Approximately 10-20% of childhood common ALL demonstrate the TEL/AML1 fusion gene resulting from the translocation t(12;21)(p13; q22). [24][25][26] This subtype of common ALL, with the TEL/AML1 fusion gene, shows a relatively good prognosis and suggests the deletion of the other TEL allele. 24,27 These findings have been confirmed by our studies.…”

Section: Discussionmentioning

confidence: 99%

“…[24][25][26] This subtype of common ALL, with the TEL/AML1 fusion gene, shows a relatively good prognosis and suggests the deletion of the other TEL allele. 24,27 These findings have been confirmed by our studies. In the present study, three of 32 patients (9.4%) with common ALL showed the TEL/AML1 fusion gene.…”

Section: Discussionmentioning

confidence: 99%

“…Most interestingly in this study, RER was preferentially located in 9p and 12p. Kim et al 24 reported that the four cell lines established from common ALL showed the TEL/AML1 chimeric genes on 12p and that among them three cell lines also showed suppression of the p16 genes on 9p. In addition, in the present study clinical samples from two patients showed DNA abnormalities of both 9p and 12p.…”

Section: Discussionmentioning

confidence: 99%

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