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A novel chromosomal translocation t(1;14)(q25;q32) in pre-B acute lymphoblastic leukemia involves the LIM homeodomain protein gene, Lhx4

Oncogene volume 21, pages 4983–4991 (2002)Cite this article

Abstract

Chromosome 1q21-25 is one of the hotspots of chromosomal abnormalities including translocations and duplications in hematological malignancies. This would suggest that oncogene(s) reside in this region. We have cloned the junctional sequence of t(1;14)(q25;q32) in pre-B acute lymphoblastic leukemia cells by an inverse PCR method. A novel sequence was fused to the joining region of the immunoglobulin heavy chain gene. We confirmed this rearrangement by Southern blot analysis, genomic PCR and fluorescence in situ hybridization. We found a coding sequence which is homologous to the mouse Lhx4 cDNA sequence 17 kb from the breakpoint. The human Lhx4 gene encodes 390 amino-acids, including one tandem pair of LIM domains and one homeodomain. The human Lhx4 gene consists of six exons. Lhx4 protein is very homologous to human Lhx3 protein except in the N-terminal region. The transcripts of the Lhx4 gene were not detected in adult multiple tissues analysed by Northern blotting, but were detected in the leukemic cells carrying t(1;14)(q25;q32) by reverse-transcription PCR. The protein expression of Lhx4 in these leukemic cells was confirmed by Western blot analysis. Lhx4 activated the reporter gene carrying the mouse α-glycoprotein subunit promoter region, which is regulated by Lhx3. LIM protein and homeodomain protein genes are frequently involved in translocations of hematological malignancies. The Lhx4 gene is deregulated in the leukemic cells and Lhx4 protein may play an important role, possibly as an activator, in leukemogenesis.

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Acknowledgements

We thank Ms Koshimura, Ms Wakairo, Ms Hayashi and Ms Ohyanagi for technical help. We also thank Dr GN Gill and Dr J Rhodes for the expression vectors, and Dr SL Pfaff for antibody specific to mouse Lhx4. We also thank Dr RV Llyod for the pituitary adenoma cell line, HP75.

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-8421, Tokyo, Japan

    Norihiko Kawamata, Sakura Sakajiri, Kei-ji Sugimoto, Yasushi Isobe, Hirofumi Kobayashi & Kazuo Oshimi

  2. Division of Hematology, Department of Medicine, Saitama Cancer Center, 818 Komuro, Ina, 362-0806, Saitama, Japan

    Hirofumi Kobayashi

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  1. Norihiko Kawamata
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  2. Sakura Sakajiri
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  3. Kei-ji Sugimoto
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  4. Yasushi Isobe
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  5. Hirofumi Kobayashi
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  6. Kazuo Oshimi
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Corresponding author

Correspondence to Norihiko Kawamata.

Additional information

The Genebank accession number of the junctional sequence between IgH and Lhx4 is AF416729 and the cDNA sequence of human Lhx4 is AY053457.

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Kawamata, N., Sakajiri, S., Sugimoto, Kj. et al. A novel chromosomal translocation t(1;14)(q25;q32) in pre-B acute lymphoblastic leukemia involves the LIM homeodomain protein gene, Lhx4. Oncogene 21, 4983–4991 (2002). https://doi.org/10.1038/sj.onc.1205628

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