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Acute Leukemias

E2A-ZNF384 and NOL1-E2A fusion created by a cryptic t(12;19)(p13.3; p13.3) in acute leukemia

Leukemia volume 22, pages 723–729 (2008)Cite this article

Abstract

A 5-year-old boy who initially presented with ALL and relapsed 4 months later with AML was found to have an add(19) in the leukemia cells. FISH revealed that the add(19) was really a cryptic t(l2;l9)(p13.3;p13.3) interrupting E2A (TCF3). Nucleotide sequences of cloned genomic fragments with the E2A rearrangements revealed that the der(12) contained E2A joined to an intron of the NOLI (p120) gene. Reverse transcriptase (RT)–PCR of patient lymphoblast RNA showed expression of in-frame fusion cDNAs consisting of most of NOL1 fused to the 3′ portion of E2A that encoded part of the second transcriptional activation domain and the DNA binding and protein dimerization motifs. The reciprocal der(19) E2A genomic rearrangements included 5′ regions of E2A joined to an intron of the ZNF384 (NMP4, CIZ) gene, located approximately 450 kb centromeric to NOL1 on chromosome 12. RT–PCR showed expression of in-frame E2A-ZNF384 fusion cDNAs. To our knowledge, this is the second report of a chromosome translocation in leukemia resulting in two different gene fusions. This is the first report of expression of E2A fusion protein that includes the DNA binding and protein dimerization domains due to a more proximal break in E2A compared to those described previously.

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Acknowledgements

This work was supported by grants from The American Cancer Society (LBC 97-463), the Loewenstern Family Foundation and the Pediatric Cancer Foundation to SPH and NCI Cancer Center Core Grant CA 46934.

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Authors and Affiliations

  1. Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA

    C-h Zhong, V Prima, C Frye & S P Hunger

  2. Department of Pediatrics, University of Florida Shands Cancer Center, Gainesville, FL, USA

    C-h Zhong, V Prima, C Frye & S P Hunger

  3. Department of Pathology, University of Colorado School of Medicine, Aurora, CO, USA

    X Liang, L McGavran & L Meltesen

  4. University of Colorado Cancer Center, Denver, CO, USA

    L McGavran & M Varella-Garcia

  5. The Children's Hospital, Denver, CO, USA

    Q Wei & S P Hunger

  6. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA

    T Boomer, J Gump & S P Hunger

  7. Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA

    M Varella-Garcia

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  1. C-h Zhong
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Correspondence to S P Hunger.

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Zhong, Ch., Prima, V., Liang, X. et al. E2A-ZNF384 and NOL1-E2A fusion created by a cryptic t(12;19)(p13.3; p13.3) in acute leukemia. Leukemia 22, 723–729 (2008). https://doi.org/10.1038/sj.leu.2405084

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