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NCOA3, a new fusion partner for MOZ/MYST3 in M5 acute myeloid leukemia

Leukemia volume 22, pages 663–665 (2008)Cite this article

The recurrent translocation t(8;16)(p11;p13) is found in about 6.5% of acute myeloid leukemias (AMLs) of the M4/M5-FAB subtypes. These poor prognosis AMLs are associated with erythrophagocytosis by blast cells. The translocation results in the fusion of the MYST3 gene (also known as MOZ) on chromosome region 8p11 to the CREBBP gene (also known as CBP) on chromosome region 16p13.1, 2, 3 In the same type of AML, the t(10;16)(q22;p13) fuses MYST3-homolog MYST4 to CREBBP4 and the t(8;22)(p11;q13) fuses MYST3 to CREBBP-homolog EP300.5 MYST3, MYST4, CREBBP and EP300 encode transcriptional regulators and acetyltransferases. MYST3 is also fused to NCOA2 in the inv(8)(p11q13).6, 7 NCOA1/SRC1, NCOA2/TIF2 and NCOA3 are paralogous genes encoding transcription coactivators of the p160 family.8 Some rearrangements involving NCOA genes and MYST3 or MYST4 genes have not been reported yet, but have been suspected or predicted on the basis of homology relations.4 We report here a new type of translocation, t(8;20)(p11;q13), which occurs in an M5-AML and fuses MYST3 to NCOA3.

Based on hematology (FAB subtype) and homology,4 we suspected the involvement of MYST3 and NCOA3 in the translocation. We demonstrated the involvement of these loci by using dual-color fluorescence in situ hybridization (FISH) on metaphases of AML-BM cells, using labeled-BAC clones, as previously described4, 7 (Figure 1b). The MYST3–NCOA3 gene fusion was confirmed by using PCR amplification of retrotranscribed mRNA from BM cells of the patient, as previously described.7 The two wild-type and the two fusion transcripts were amplified (Figure 1c) using MYST3 and NCOA3 primer sequences (available on demand). The breakpoint in MYST3 occurs in intron-17, as in MYST3–CREBBP (type I) and MYST3–NCOA2.3, 6 The breakpoint in NCOA3 is located at nucleotides 2752 and 2376 in the MYST3–NCOA3 and NCOA3–MYST3 fusion transcripts, respectively. It occurs in exon 13, which is truncated of 45 base pairs. Only the MYST3–NCOA3 fusion transcript has an open reading frame that may generate a functional chimeric protein. As in MYST3–NCOA2, the CREB-interacting domain in NCOA3 (1046–1092 aa) is conserved in the putative MYST3–NCOA3 fusion protein (at positions 1246–1292 aa) suggesting a similar potential oncogenic role in targeting the transcription machinery in AML-M4/M5 involving MYST3, MYST4 or MLL fusions (Figure 1d).

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Acknowledgements

This work was supported by Inserm and Institut Paoli-Calmettes.

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Authors and Affiliations

  1. Laboratoire d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, UMR599 Inserm, Institut Paoli-Calmettes, Marseille, France

    S Esteyries, J Adelaide, A Lagarde, S Olschwang, D Birnbaum, M Chaffanet & M-J Mozziconacci

  2. Laboratoire de Cytogénétique, Hôpital Saint-Antoine, Paris, France

    C Perot

  3. Laboratoire d’Hématologie, Hôpital Henri Mondor, Créteil, France

    M Imbert

  4. Service d’Hématologie Clinique, Hôpital Henri Mondor, Créteil, France

    C Pautas

  5. Département de BioPathologie, Institut Paoli-Calmettes, Marseille, France

    M-J Mozziconacci

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  1. S Esteyries
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Correspondence to M-J Mozziconacci.

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Esteyries, S., Perot, C., Adelaide, J. et al. NCOA3, a new fusion partner for MOZ/MYST3 in M5 acute myeloid leukemia. Leukemia 22, 663–665 (2008). https://doi.org/10.1038/sj.leu.2404930

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