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Acute myeloid leukemia with t(7;21)(q11.2;q22) expresses a novel, reversed-sequence RUNX1–DTX2 chimera

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Abstract

The RUNX1 gene is frequently rearranged in acute leukemia. We cloned a novel RUNX1 chimeric gene generated by t(7;21)(q11.2;q22) in a patient with acute myeloid leukemia. 3′-rapid amplification of cDNA ends analysis showed a tail-to-tail fusion between RUNX1 on 21q22 and DTX2 on 7q11.2, with an insertion of short complementary sequence from UPK3B adjacent to DTX2. DTX2 encodes a putative E3-ubiquitin ligase with no known biological function. There are two possible functions of RUNX1-reversed UPK3B–DTX2: one from aberrant RUNX1 chimeric protein and the other from the reversed sequence of DTX2. The predicted aberrant protein expressed under the RUNX1 promoter was highly structurally similar to RUNX1a. In a reporter assay, the aberrant protein inhibited the trans-activation function of RUNX1 in a dominant-negative manner, similar to RUNX1a. In contrast, the DTX2 reversed sequence may degrade wild-type DTX2 transcript or suppress its translation. In conclusion, we identified a novel fusion RUNX1 partner, DTX2, which chimerize in a reverse direction. This is the first example of RUNX1 chimera in an opposing direction generated by chromosomal translocation in leukemia. In addition to the aberrantly truncated RUNX1 protein, the DTX2 antisense sequence may play some role in the development of leukemia carrying the t(7;21) translocation.

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Acknowledgments

We thank Dr. Yuko Sato for generously providing us a genomic probe set for RUNX1 gene (YR9 and Y133). We also thank Drs. M. Ishimae and M. Eguchi for reviewing the metaphase and Ms. A. Okada for her special technical assistance. This work was financially supported by the Grants-in-Aid from the Ministries in Japan of Education, Culture, Sports, Science and Technology (17016068), and Health, Labour and Welfare, Japanese Society for the Promotion of Science (20390275, 18591086, 50337391) and Seki Minato Award from Dokkyo Medical University School of Medicine.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi, 321-0293, Japan

    Kazuhiro Maki, Ko Sasaki, Fusako Sugita, Yuka Nakamura & Kinuko Mitani

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  1. Kazuhiro Maki
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  2. Ko Sasaki
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  3. Fusako Sugita
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  4. Yuka Nakamura
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  5. Kinuko Mitani
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Correspondence to Kinuko Mitani.

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Maki, K., Sasaki, K., Sugita, F. et al. Acute myeloid leukemia with t(7;21)(q11.2;q22) expresses a novel, reversed-sequence RUNX1–DTX2 chimera. Int J Hematol 96, 268–273 (2012). https://doi.org/10.1007/s12185-012-1112-z

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  • DOI: https://doi.org/10.1007/s12185-012-1112-z

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