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Translocation t(1;16)(p31;q24) rearranging CBFA2T3 is specific for acute erythroid leukemia

Leukemia volume 25, pages 1510–1512 (2011)Cite this article

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Acute erythroid leukemias are characterized by a predominantly erythroid population of bone marrow cells. Most authors agree that two main subtypes exist: (1) erythroleukemia (erythroid/myeloid) or acute myeloid leukemia (AML) M6a, according to the French-American-British criteria,1, 2 in which >50% erythroid precursors in the entire nucleated cell population and >20% myeloblasts in the non-erythroid cell population are found, and (2) pure erythroid leukemia or AML M6b, according to the French-American-British classification,1, 2 in which erythroblasts constitute more than 80% of the bone marrow cells with no significant myeloblastic component.1, 2, 3 Whereas erythroleukemia (erythroid/myeloid) is predominantly a disease of adults and comprises 5–6% of all cases of AML,4 pure erythroid leukemia is extremely rare, is usually associated with a rapid clinical course and can occur in all age groups.5 The Mitelman database of chromosome aberrations and gene fusions in cancer provides karyotypic information on about 600 cases of acute erythroid leukemia.6 The most common aberrations are structural and numerical changes of chromosomes 5 and 7, followed by trisomy 8. These aberrations are common also in other AML subtypes,7 however, and indeed it seems that no specific chromosomal aberration or pathogenetic mechanism (for example, fusion gene or gene deregulation) leading to erythroid leukemia has been reported.

To identify the exact breakpoint on the der(16q), appropriate fosmid clones were selected inside the region chr16:87 493 639–87 591 195 (16q24), as this was where the breakpoint lay based on bacteria artificial chromosomes data. Only one gene is present in this region, the core-binding factor, runt-domain, alpha subunit 2 translocated to 3 (CBFA2T3, previously known as MTG16, myeloid translocation gene). The breakpoint on chromosome 16 was identified inside the big intron 1 of the CBFA2T3 gene. CBFA2T3 encodes a protein in the myeloid translocation gene family of transcriptional co-repressors. Recombination of CBFA2T3 with the RUNX1 gene has been demonstrated in six cases of AML with a t(16;21)(q24;q22)9 and then with the CBFA2T3 breakpoint either between exons 1 and 2 or between exons 3 and 4. The fusion retains four evolutionarily conserved motifs, that is, NHR1, NHR2, NHR3 and the zinc finger domain NHF4.9 In our case, the breakpoint was in intron 1, thus making the product of the rearrangement similar to that previously described.

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Acknowledgements

This work was supported by grants from the Norwegian Cancer Society and the South-East Norway Regional Health Authority. We thank Roberta Roberto, Tiziana Storlazzi, Hege Kilen Andersen and Marthe Løvf for their technical support.

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Authors and Affiliations

  1. Section for Cancer Cytogenetics, Institute for Medical Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway

    F Micci, J Thorsen, L Haugom & S Heim

  2. Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway

    F Micci, J Thorsen, L Haugom & S Heim

  3. Department of Pediatrics, Rikshospitalet, Oslo University Hospital, Oslo, Norway

    B Zeller

  4. Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Norway

    A Tierens

  5. Faculty of Medicine, University of Oslo, Oslo, Norway

    S Heim

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Micci, F., Thorsen, J., Haugom, L. et al. Translocation t(1;16)(p31;q24) rearranging CBFA2T3 is specific for acute erythroid leukemia. Leukemia 25, 1510–1512 (2011). https://doi.org/10.1038/leu.2011.100

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